A family of structurally related proteins that are constitutively expressed and that negatively regulate cytokine-mediated SIGNAL TRANSDUCTION PATHWAYS. PIAS proteins inhibit the activity of signal transducers and activators of transcription.
An enzyme of the oxidoreductase class primarily found in PLANTS. It catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives.
An enzyme that catalyzes the oxidation of arachidonic acid to yield 5-hydroperoxyarachidonate (5-HPETE) which is rapidly converted by a peroxidase to 5-hydroxy-6,8,11,14-eicosatetraenoate (5-HETE). The 5-hydroperoxides are preferentially formed in leukocytes.
An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in PLATELETS.
Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES.
An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy-5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in NEUTROPHILS and LYMPHOCYTES.
Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates. These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids. The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- .
Compounds that bind to and inhibit the action of 5-LIPOXYGENASE-ACTIVATING PROTEINS.
A lipoxygenase metabolite of ARACHIDONIC ACID. It is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumor cell metastatic potential through activation of protein kinase C. (J Pharmacol Exp Ther 1995; 274(3):1545-51; J Natl Cancer Inst 1994; 86(15):1145-51)
Scaffolding proteins that play an important role in the localization and activation of 5-LIPOXYGENASE.
A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system.
A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils.
Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes.
The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990)
An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.
A 1.5-kDa small ubiquitin-related modifier protein that can covalently bind via an isopeptide link to a number of cellular proteins. It may play a role in intracellular protein transport and a number of other cellular processes.
A dual inhibitor of both cyclooxygenase and lipoxygenase pathways. It exerts an anti-inflammatory effect by inhibiting the formation of prostaglandins and leukotrienes. The drug also enhances pulmonary hypoxic vasoconstriction and has a protective effect after myocardial ischemia.
A class of structurally related proteins of 12-20 kDa in size. They covalently modify specific proteins in a manner analogous to UBIQUITIN.
A type of POST-TRANSLATIONAL PROTEIN MODIFICATION by SMALL UBIQUITIN-RELATED MODIFIER PROTEINS (also known as SUMO proteins).
A plant genus of the family POACEAE. Finger millet or raggee (E. coracana) is an important food grain in southern Asia and parts of Africa.
A 20-carbon unsaturated fatty acid containing 4 alkyne bonds. It inhibits the enzymatic conversion of arachidonic acid to prostaglandins E(2) and F(2a).
(2S-(2 alpha,3 beta(1E,3E,5Z,8Z)))-3-(1,3,5,8-Tetradecatetraenyl)oxiranebutanoic acid. An unstable allylic epoxide, formed from the immediate precursor 5-HPETE via the stereospecific removal of a proton at C-10 and dehydration. Its biological actions are determined primarily by its metabolites, i.e., LEUKOTRIENE B4 and cysteinyl-leukotrienes. Alternatively, leukotriene A4 is converted into LEUKOTRIENE C4 by glutathione-S-transferase or into 5,6-di-HETE by the epoxide-hydrolase. (From Dictionary of Prostaglandins and Related Compounds, 1990)
Proteins that bind to and transfer CHOLESTEROL ESTERS between LIPOPROTEINS such as LOW-DENSITY LIPOPROTEINS and HIGH-DENSITY LIPOPROTEINS.
Eighteen-carbon essential fatty acids that contain two double bonds.
A class of compounds named after and generally derived from C20 fatty acids (EICOSANOIC ACIDS) that includes PROSTAGLANDINS; LEUKOTRIENES; THROMBOXANES, and HYDROXYEICOSATETRAENOIC ACIDS. They have hormone-like effects mediated by specialized receptors (RECEPTORS, EICOSANOID).
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A genus of beetles which infests grain products. Its larva is called mealworm.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Transport proteins that carry specific substances in the blood or across cell membranes.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
The rate dynamics in chemical or physical systems.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
A homologous group of endogenous CYSTEINE PROTEINASE INHIBITORS. The cystatins inhibit most CYSTEINE ENDOPEPTIDASES such as PAPAIN, and other peptidases which have a sulfhydryl group at the active site.
A group of LEUKOTRIENES; (LTC4; LTD4; and LTE4) that is the major mediator of BRONCHOCONSTRICTION; HYPERSENSITIVITY; and other allergic reactions. Earlier studies described a "slow-reacting substance of ANAPHYLAXIS" released from lung by cobra venom or after anaphylactic shock. The relationship between SRS-A leukotrienes was established by UV which showed the presence of the conjugated triene. (From Merck Index, 11th ed)
A family of soil bacteria. It also includes some parasitic forms.
Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension.
A doubly unsaturated fatty acid, occurring widely in plant glycosides. It is an essential fatty acid in mammalian nutrition and is used in the biosynthesis of prostaglandins and cell membranes. (From Stedman, 26th ed)
A group of FLAVONOIDS characterized with a 4-ketone.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.
Trihydroxy derivatives of eicosanoic acids. They are primarily derived from arachidonic acid, however eicosapentaenoic acid derivatives also exist. Many of them are naturally occurring mediators of immune regulation.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.
A plant species of the genus SOLANUM, family SOLANACEAE. The starchy roots are used as food. SOLANINE is found in green parts.
Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds.
Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A heterogeneous mixture of glycoproteins responsible for the gel structure of egg white. It has trypsin-inhibiting activity.
A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Established cell cultures that have the potential to propagate indefinitely.
An annual legume. The SEEDS of this plant are edible and used to produce a variety of SOY FOODS.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A 6.6-kDa protein component of VERY-LOW-DENSITY LIPOPROTEINS; INTERMEDIATE-DENSITY LIPOPROTEINS; and HIGH-DENSITY LIPOPROTEINS. Apo C-I displaces APO E from lipoproteins, modulate their binding to receptors (RECEPTORS, LDL), and thereby decrease their clearance from plasma. Elevated Apo C-I levels are associated with HYPERLIPOPROTEINEMIA and ATHEROSCLEROSIS.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
Enzymes that catalyze the endohydrolysis of 1,4-alpha-glycosidic linkages in STARCH; GLYCOGEN; and related POLYSACCHARIDES and OLIGOSACCHARIDES containing 3 or more 1,4-alpha-linked D-glucose units.
Substances used to lower plasma CHOLESTEROL levels.
Derivatives of oxazolidin-2-one. They represent an important class of synthetic antibiotic agents.
A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.
Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.
A eukayrotic protein serine-threonine phosphatase subtype that dephosphorylates a wide variety of cellular proteins. The enzyme is comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist due to the presence of multiple genes and the alternative splicing of their mRNAs. A large number of proteins have been shown to act as regulatory subunits for this enzyme. Many of the regulatory subunits have additional cellular functions.
A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in NERVE TISSUE.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A signal transducer and activator of transcription that mediates cellular responses to INTERFERONS. Stat1 interacts with P53 TUMOR SUPPRESSOR PROTEIN and regulates expression of GENES involved in growth control and APOPTOSIS.
Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure.
One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.
A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and CHYMOPAPAIN that is used as a topical enzymatic debriding agent. EC 3.4.22.2.
A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. Although they take part in the assembly process, molecular chaperones are not components of the final structures.
Proteins prepared by recombinant DNA technology.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The conjugation product of LEUKOTRIENE A4 and glutathione. It is the major arachidonic acid metabolite in macrophages and human mast cells as well as in antigen-sensitized lung tissue. It stimulates mucus secretion in the lung, and produces contractions of nonvascular and some VASCULAR SMOOTH MUSCLE. (From Dictionary of Prostaglandins and Related Compounds, 1990)
Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Cell-surface receptors that bind LEUKOTRIENES with high affinity and trigger intracellular changes influencing the behavior of cells. The leukotriene receptor subtypes have been tentatively named according to their affinities for the endogenous leukotrienes LTB4; LTC4; LTD4; and LTE4.
Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A class of phenolic acids related to chlorogenic acid, p-coumaric acid, vanillic acid, etc., which are found in plant tissues. It is involved in plant growth regulation.
A family of multisubunit cytoskeletal motor proteins that use the energy of ATP hydrolysis to power a variety of cellular functions. Dyneins fall into two major classes based upon structural and functional criteria.
A group of 1,2-benzenediols that contain the general formula R-C6H5O2.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
7-carbon saturated monocarboxylic acids.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Eighteen-carbon essential fatty acids that contain three double bonds.
Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.
A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A biologically active principle of SRS-A that is formed from LEUKOTRIENE D4 via a peptidase reaction that removes the glycine residue. The biological actions of LTE4 are similar to LTC4 and LTD4. (From Dictionary of Prostaglandins and Related Compounds, 1990)
Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Compounds based on benzeneacetamide, that are similar in structure to ACETANILIDES.
A family of heterotrimeric GTP-binding protein alpha subunits that were originally identified by their ability to inhibit ADENYLYL CYCLASES. Members of this family can couple to beta and gamma G-protein subunits that activate POTASSIUM CHANNELS. The Gi-Go part of the name is also spelled Gi/Go.
Elements of limited time intervals, contributing to particular results or situations.
FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Immature ERYTHROCYTES. In humans, these are ERYTHROID CELLS that have just undergone extrusion of their CELL NUCLEUS. They still contain some organelles that gradually decrease in number as the cells mature. RIBOSOMES are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic "reticulum" (not the same as the ENDOPLASMIC RETICULUM), hence the name reticulocytes.
A cell line derived from cultured tumor cells.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
A group of compounds that contain the structure SO2NH2.
The sum of the weight of all the atoms in a molecule.
A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.
A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain. Bovine kinesin is a heterotetramer composed of two heavy (120 kDa) and two light (62 kDa) chains. EC 3.6.1.-.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A class of cell surface leukotriene receptors with a preference for leukotriene B4. Leukotriene B4 receptor activation influences chemotaxis, chemokinesis, adherence, enzyme release, oxidative bursts, and degranulation in polymorphonuclear leukocytes. There are at least two subtypes of these receptors. Some actions are mediated through the inositol phosphate and diacylglycerol second messenger systems.
A stable, physiologically active compound formed in vivo from the prostaglandin endoperoxides. It is important in the platelet-release reaction (release of ADP and serotonin).
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Eighteen-carbon cyclopentyl polyunsaturated fatty acids derived from ALPHA-LINOLENIC ACID via an oxidative pathway analogous to the EICOSANOIDS in animals. Biosynthesis is inhibited by SALICYLATES. A key member, jasmonic acid of PLANTS, plays a similar role to ARACHIDONIC ACID in animals.
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
A creeping annual plant species of the CUCURBITACEAE family. It has a rough succulent, trailing stem and hairy leaves with three to five pointed lobes.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Dioxygenases that catalyze the peroxidation of methylene-interrupted UNSATURATED FATTY ACIDS.
A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.
The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A group of compounds that contain a bivalent O-O group, i.e., the oxygen atoms are univalent. They can either be inorganic or organic in nature. Such compounds release atomic (nascent) oxygen readily. Thus they are strong oxidizing agents and fire hazards when in contact with combustible materials, especially under high-temperature conditions. The chief industrial uses of peroxides are as oxidizing agents, bleaching agents, and initiators of polymerization. (From Hawley's Condensed Chemical Dictionary, 11th ed)
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
Agents that inhibit PROTEIN KINASES.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Presence of warmth or heat or a temperature notably higher than an accustomed norm.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.
Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.
A class of enzymes that catalyze the formation of a bond between two substrate molecules, coupled with the hydrolysis of a pyrophosphate bond in ATP or a similar energy donor. (Dorland, 28th ed) EC 6.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
One of the biologically active principles of SRS-A. It is generated from LEUKOTRIENE C4 after partial hydrolysis of the peptide chain, i.e., cleavage of the gamma-glutamyl portion. Its biological actions include stimulation of vascular and nonvascular smooth muscle, and increases in vascular permeability. (From Dictionary of Prostaglandins and Related Compounds, 1990)
Cell surface proteins that bind eicosanoids with high affinity and trigger intracellular changes influencing the behavior of cells. Among the eicosanoid receptors are receptors for the prostaglandins, thromboxanes, and leukotrienes.
A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.
A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.
A group of alicyclic hydrocarbons with the general formula R-C5H9.
Enzymes of the isomerase class that catalyze the oxidation of one part of a molecule with a corresponding reduction of another part of the same molecule. They include enzymes converting aldoses to ketoses (ALDOSE-KETOSE ISOMERASES), enzymes shifting a carbon-carbon double bond (CARBON-CARBON DOUBLE BOND ISOMERASES), and enzymes transposing S-S bonds (SULFUR-SULFUR BOND ISOMERASES). (From Enzyme Nomenclature, 1992) EC 5.3.
A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Proteins, usually acting in oxidation-reduction reactions, containing iron but no porphyrin groups. (Lehninger, Principles of Biochemistry, 1993, pG-10)
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.
7-Hydroxycoumarins. Substances present in many plants, especially umbelliferae. Umbelliferones are used in sunscreen preparations and may be mutagenic. Their derivatives are used in liver therapy, as reagents, plant growth factors, sunscreens, insecticides, parasiticides, choleretics, spasmolytics, etc.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
All-purpose surfactant, wetting agent, and solubilizer used in the drug, cosmetics, and food industries. It has also been used in laxatives and as cerumenolytics. It is usually administered as either the calcium, potassium, or sodium salt.
Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.

Involvement of 5-lipoxygenase activating protein in the amyloidotic phenotype of an Alzheimer's disease mouse model. (1/4)

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Pharmacodynamics, pharmacokinetics and safety of GSK2190915, a novel oral anti-inflammatory 5-lipoxygenase-activating protein inhibitor. (2/4)

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An inhibitor of leukotriene synthesis affects vasopressin secretion following osmotic stimulus in rats. (3/4)

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FLAP pharmacological blockade modulates metabolism of endogenous tau in vivo . (4/4)

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BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and Repair, Diabetes, Obesity and Metabolic Syndrome, Stem Cell Biology, Gene Regulation, Signal Transduction, etc. BioVisions products are currently being sold in more than 60 countries worldwide.
FLAP antibody, Internal (arachidonate 5-lipoxygenase-activating protein) for IHC-P, WB. Anti-FLAP pAb (GTX89246) is tested in Human samples. 100% Ab-Assurance.
Intracerebral injection of brain extracts containing amyloid or tau aggregates in transgenic animals can induce cerebral amyloidosis and tau pathology. We extracted pure populations of tau oligomers directly from the cerebral cortex of Alzheimer disease (AD) brain. These oligomers are potent inhibit …
Serum-alone treatment of monocytes did not induce any detectable increase in IL-1β, TNF-α or IL-6 secretion. However, pre-treatment with PFAPA-IN serum did result in significantly more IL-1β secretion following LPSup stimulation as compared to PFAPA-OUT serum pretreatment (330.8 ± 181.5 and 173.5 ± 100.1 pg/ml respectively; n=9; p,0.05). There was no modulation in the levels of TNF-α and IL-6 under the present conditions, arguing for a process specific for the IL-1β pathway. ...
Diabetic patients exhibit a reduction in β cells, which secrete insulin to help regulate glucose homeostasis; however, little is known about the factors that regulate proliferation of these cells in human pancreas. Access to primary human β cells is limited and a challenge for both functional studies and drug discovery progress. We previously reported the generation of a human β cell line (EndoC-βH1) that was generated from human fetal pancreas by targeted oncogenesis followed by in vivo cell differentiation in mice. EndoC-βH1 cells display many functional properties of adult β cells, including expression of β cell markers and insulin secretion following glucose stimulation; however, unlike primary β cells, EndoC-βH1 cells continuously proliferate. Here, we devised a strategy to generate conditionally immortalized human β cell lines based on Cre-mediated excision of the immortalizing transgenes. The resulting cell line (EndoC-βH2) could be massively amplified in vitro. After ...
Tips to survive allergy season - Every spring trees and plants release pollen into the air to fertilize other plants. The released pollen can potentially enter an individuals nasal passages and trigger an immune response. This process affects mil...
To compare the roles of soluble CLP and membrane-bound FLAP in LT biosynthesis, we knocked down these proteins in the human monocytic cell line MM6. 5LO activity was determined in cells stimulated by four different protocols. Our results indicate that the presence of CLP in MM6 cells increased 5LO activity in all conditions (Figs. 1 and 2 and Table S1). Thus, CLP can support 5LO activity in intact cells as well, complementing previous in vitro data (12, 17). CLP is not absolutely crucial, however; some 5LO activity remained in all incubations of CLP knockdown cells. FLAP knockdown had only minor effects in incubations including exogenous AA, but 5LO product formation from endogenous substrate was greatly reduced. This finding is in accordance with the ideas that FLAP has a role in providing endogenous substrate to 5LO at the nuclear membrane (6) and that exogenous AA can be converted by 5LO in a FLAP-independent manner.. When cells are stimulated to produce LTs, 5LO typically translocates to the ...
Aggregation of the microtubule‐associated protein tau is a key feature of Alzheimers disease and other so‐called tauopathies, yet what causes this protein to aggregate and what renders it toxic is only slowly being revealed. Because tau spreads in a stereotypical pattern through the diseased brain, it has been proposed that it possesses prion‐like properties, with aggregation‐prone tau facilitating the conversion of naïve tau into toxic forms. The current study by Wegmann et al (2015) addresses whether tau fulfils classical prion criteria by assessing its spreading and toxicity in the absence of endogenous tau. Using different transgenic and viral paradigms, the authors demonstrate that, although tau still propagates in this scenario, there is a decrease in its misfolding and neurotoxicity. They therefore conclude that tau is not a genuine prion, at least when the current definition of these infectious proteins is applied.. See also: S Wegmann et al (December 2015) ...
The researchers first asked how aggregation influences pathology. In the case of the full-length proaggregation form of tau, the scientists saw a pathological conformation of tau (i.e., MC1 staining) and hyperphosphorylation at many sites in the hippocampus after 6 months, but no tangle formation. They saw only minor changes in phosphorylation with the antiaggregation mutant. All changes were reversible when tau expression was switched off for 6 weeks. In the case of the short form of tau, the proaggregation mutant began developing tangles in the entorhinal cortex at 3 months and progressed with age, even at low levels of exogenous tau (0.7 of endogenous), whereas the antiaggregation mutants showed no tangles. The proaggregation short form of tau nucleated aggregates, which then grew to incorporate both transgenic and endogenous tau. In old mice, the proaggregation, but not the antiaggregation mutants caused synaptic loss and neurodegeneration in the dentate gyrus of the hippocampus. In ...
The prediabetic state is characterized by normal glucose tolerance but decreased insulin secretion following glucose stimulation. In spite of our earlier beliefs, this state is not always devoid of metabolic consequences. Thus, the disappearance rate of intravenously administered glucose (k-value), although within the normal range, is significantly lower than in the control group. In a few prediabetics the regulation of hepatic glucose output resembles that of diabetics. In some, the lipolytic response to physical exercise is increased to the extent found in manifest diabetes. Furthermore, prediabetic mothers may give birth to children with diabetic fetopathy. Many of the newborns of these women show high k-values as do children of diabetic women.. The decreased insulin output of prediabetics and mild diabetics is probably due to a decreased sensitivity for glucose of a specific receptor of the beta cells of the pancreas. This suggestion is supported by the finding that both prediabetics and ...
Colostrum Colostrum is the first mammary secretion following the birth of a newborn, prior to lactation. Its properties are highly beneficial for health, growth, development and immune system functions. Bovine Colostrum is nearly identical to human Colostrum, and can benefit growth and immunity, muscle mass development, and bone and joint health in children and adults of all ages. Bovine Colostrum, is used for immune system enhancement, antibacterial, viral, and fungal protection, anti-inflammatory effects, wound healing, gastrointestinal problems, allergies, fatigue and muscle pain relief, to promote growth and muscle mass development and to promote bone and joint health. Collected from U.S. pasture-fed cows, FoodScience Colostrum is pesticide, antibiotic, and hormone free. Each enteric coated capsule contains: 600 mg Bovine Colostrum Ig (Immunoglobulins) 180 mg. Other ingredients: gelatin, water. As a dietary supplement, take 1 capsule on a empty stomach, one to three times daily. This statement has
"Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice ... Zileuton is a specific inhibitor of 5-lipoxygenase and thus inhibits leukotriene (LTB4, LTC4, LTD4, and LTE4) formation. Both ... Another important activity for hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase [59]. Moreover, this ... is a medication which functions as a leukotriene-related enzyme inhibitor (arachidonate 5-lipoxygenase) or leukotriene receptor ...
Unlike common variants, mutations causing rare diseases tend to be in the regions of genes that encode proteins, providing both ... activated a system to isolate anyone diagnosed with the virus and to trace and quarantine all of their contacts. Iceland's ... 5, no 1 February 2011, pp. 50-65 On deCODE in the context of the new genomics: Davies, Kevin, The $1,000 Genome: The Revolution ... 5 January 2017 C Brownstein, et al., "If I knew then what I know now: The need for infrastructure to enable precision medicine ...
"Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein". Science. 317 (5837): 510-2. Bibcode:2007Sci... ... How FLAP activates 5-lipooxygenase is not completely understood, but there is a physical interaction between the two. FLAP ... It is an integral protein within the nuclear membrane. FLAP is necessary in synthesis of leukotriene, which are lipid mediators ... Leukotrienes, which need the FLAP protein to be made, have an established pathological role in allergic and respiratory ...
This protein is involved in the production of cysteinyl leukotrienes which are involved in inflammation, and AM-679 has anti- ... AM-679 is a drug which acts as a selective inhibitor of 5-Lipoxygenase-activating protein (FLAP). ... a potent FLAP inhibitor". Bioorganic & Medicinal Chemistry Letters. 20 (1): 213-7. doi:10.1016/j.bmcl.2009.10.131. PMID ... Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H- ...
BLT2 receptors, similar to BLT1 receptors, are G protein coupled receptors that, when ligand-bound, activate G proteins that ... adenocarcinoma cells in culture was stimulated by 12-HETE and inhibited by a somewhat selective inhibitor of 12-lipoxygenase, ... "Induction of cyclooxygenase-2 by activated Ha-ras oncogene in Rat-1 fibroblasts and the role of mitogen-activated protein ... thereby activating calcium-activated intracellular signaling molecules; it also stimulates cells to activate Extracellular ...
... and/or 271 by Mitogen-activated protein kinases, S6 kinase, protein kinase A (PKA), protein kinase C, Cdc2, and/or a Ca2+/ ... neither LTB4 synthesis inhibitors (i.e. blockers of ALOX5 or LTA4 hydrolase) nor inhibitors of LTB4 receptors (BLT1 and BLT2) ... ALOX5 binds with the F actin-binding protein, coactin-like protein. Based on in vitro studies, this protein binding serves to ... This chemotactic factor stimulation concurrently causes the activation of mitogen-activated protein kinases (MAPK) which in ...
... activate cells by releasing the Gq alpha subunit and pertussis toxin-sensitive Gi alpha subunit from Heterotrimeric G proteins ... Fourie, A. M. (2009). "Modulation of inflammatory disease by inhibitors of leukotriene A4 hydrolase". Current Opinion in ... and lipoxygenase-derived eicosanoids". Drug Metabolism and Disposition. 39 (2): 180-90. doi:10.1124/dmd.110.035121. PMC 3033693 ... but also bound and was activated by a wide range of peptides, proteins, and other agents. BLT2 may ultimately prove to have ...
Huntingtin Interacting protein 1) Hsp70 Histactophilin Hsp90 Histidine rich protein II Hsp100 Inhibitor of apoptosis (IAP) ... p21-activated Kinase) Plectin p47PHOX Parvin (actopaxin) Prefoldin p53 PASK (Proline, Alanine rich Ste20 related Kinase) ... Actin-binding proteins (also known as ABPs) are proteins that bind to actin. This may mean ability to bind actin monomers, or ... This is a list of actin-binding proteins in alphabetical order. List: 0-9 A B C D E F G H I J K L M N O P Q R S T U V W x Y Z ...
Other lipoxygenases-8-LO, 12-LO and 15-LO-make other eicosanoid-like products. To act, 5-LO uses the nuclear-membrane enzyme 5- ... lipoxygenase-activating protein (FLAP), first to a hydroperoxyeicosatetraenoic acid (HPETE), then to the first leuokotriene, ... Increasing DGLA intake may allow DGLA to act as a competitive inhibitor of 2-series PGs and 4-series LTs and thus suppress ... They activate phospholipidase to release AA from neuron cell membranes as a free fatty acid. During its short lifespan, free AA ...
It can be activated at sites of tissue injury or sites of inflammation directly by endogenous mediators or indirectly as a ... While the earliest inhibitors, such as HC-030031, were lower potency (micromolar inhibition) and had limited TRPA1 specificity ... One of the specific functions of this protein studies involves a role in the detection, integration and initiation of pain ... May 2013). "Systematic analysis of rat 12/15-lipoxygenase enzymes reveals critical role for spinal eLOX3 hepoxilin synthase ...
... inhibitor of 12-lipoxygenase but not other human lipoxygenases. This effect could also have anti-inflammatory and anti- ... 15(S)-HpETE and 15(S)-HETE bind to and activate the G protein-coupled receptor, Leukotriene B4 receptor 2, i.e. BLT2. This ... 15-Lipoxygenase-2: Cells also used 15-lipoxygenase 2 (i.e. 15-LOX-2 or ALOX15B) to make 15(S)-HpETE and 15(S)-HETE. However ... 15-Lipoxygenase-1: Cells metabolize arachidonic acid with 15-lipoxygenase-1 (i.e., 15-LO-1, ALOX15) to form 15(S)-HpETE as a ...
The protein biology approach to this research involved trying to map complex processes using limited samples, mainly of brain ... It has been widely cited and used to inform the development of BACE1 inhibitors as potential treatments. Stefansson and the ... Genes encode proteins, so identifying the genes and specific genetic variations that patients tended to share more often than ... Although publishing steadily, Stefansson was frustrated by the pace of progress and often by not knowing whether the proteins ...
Receptors that activate this pathway are mainly G protein-coupled receptors coupled to the Gαq subunit, including: 5-HT2 ... Huang W, Barrett M, Hajicek N, Hicks S, Harden TK, Sondek J, Zhang Q (February 2013). "Small molecule inhibitors of ... and the lipoxygenase pathway (producing leukotrienes (LTB4, LTC4, LTD4, LTE4)). The bacterial variant Clostridium perfringens ... In addition, calcium and DAG together work to activate protein kinase C, which goes on to phosphorylate other molecules, ...
Meconium can also activate the coagulation cascade, production of platelet-activating factor (PAF) and other vasoactive ... However, COX inhibitors may induce peptic ulcers and cause hyperkalemia and hypernatremia. Additionally, COX inhibitors have ... Surfactant is synthesised by type II alveolar cells and is made of a complex of phospholipids, proteins and saccharides. It ... Arachidonic acid is metabolised, via cyclooxygenase (COX) and lipoxygenase, to various substances including prostaglandins and ...
CysLTR1 is a G protein-coupled receptor that links to and when bound to its CysLT ligands activates the Gq alpha subunit and/or ... Haeggström JZ, Funk CD (October 2011). "Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease". ... and drug inhibitors of CysLTR1 block the in vivo and in vivo (animal model) growth of CRC cells and tumors, respectively. The ... Acting through these G proteins and their subunits, ligand-bound CysLTR1 activates a series of pathways that lead to cell ...
"Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice ... "The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing". Nature Cell ... It may perform this by blocking the 5-lipoxygenase activating protein (FLAP), thus inhibiting 5-lipoxygenase (5-LOX),[1] and ... 3-[3-butylsulfanyl-1-[(4-chlorophenyl)methyl]-5-propan-2-yl-indol-2-yl]-2,2 -dimethyl-propanoic acid ...
Cannabidiol, a FAAH inhibitor, increases levels in anandamide and may have antipsychotic effect; though results are mixed here ... The lipoxygenase-5 inhibitor minocycline has been seen to be marginally effective in halting schizophrenia progression. One of ... Okada, F.; Crow, T. J.; Roberts, G. W. (1990). "G-proteins (Gi, Go) in the basal ganglia of control and schizophrenic brain". ... Similarly, toxoplasmosis infection in the CNS (positively correlated to schizophrenia) activates inflammatory cascades, also ...
J Neurosci Res 24:558-566, 1989 Squinto SP, Braquet P, Block AL, Bazan NG: Platelet-activating factor activates HIV promoter in ... Research led by Bazan in 2015 also discovered a protein in the retina that is crucial for vision. Bazan and his colleagues ... NeuroReport 12:53-57, 2001 Bazan NG, Birkle DL, Reddy TS: Docosahexaenoic acid (22:6, n 3) is metabolized to lipoxygenase ... This included the finding that seizure-induced platelet-activating factor production activates gene expression, as well as a ...
... cyclic adenosine monophosphate response element-binding protein phosphorylation, and p38 mitogen-activated protein kinase ... Delta12-lipoxygenase, 12Delta-lipoxygenase, and C-12 lipoxygenase. ALOX12, often termed plate platelet-type 12-lipoxygenase, is ... A selective but not totally specific inhibitor of ALOX12 reduced the growth response of cultured human endothelial cells to ... ALOX12 (EC 1.13.11.31), also known as arachidonate 12-lipoxygenase, 12-lipoxygenase, 12S-Lipoxygenase, 12-LOX, and 12S-LOX is a ...
Since it mediates the action of 12(S)-HETE in stimulating cultured PC3 cells to activate the Mitogen-activated protein kinase ... Tong, W. G.; Ding, X. Z.; Adrian, T. E. (2002). "The mechanisms of lipoxygenase inhibitor-induced apoptosis in human breast ... HETE in activating the Mitogen-activated protein kinase kinase/Extracellular signal-regulated kinases-1/2 pathway and NFκB ... stimulates PC3 cells to activate the Mitogen-activated protein kinase kinase/extracellular signal-regulated kinases-1/2 pathway ...
... structure of the catalytic domain of porcine leukocyte 12-lipoxygenasean with inhibitor UMich Orientation of Proteins in ... and thereby are key regulators in the formation of lipoxygenase-dependent metabolites. In addition, cells, when so activated, ... erythrocyte type 15-lipoxygenase (or 15-lipoxygenase, erythrocyte type), reticulocyte type 15-lipoxygenase (or 15-lipoxygenase ... LOX-DB - LipOXygenases DataBase Lipoxygenases iron-binding region in PROSITE PDB: 1YGE​ - structure of lipoxygenase-1 from ...
... metabolites many of which act on cells by binding with and thereby activating specific and well-characterized receptor proteins ... Finally, there are relatively few metabolite-forming lipoxygenases and cyclooxygenases in the first and second pathways and ... certain proton pump inhibitor and antidepressant drugs.[unreliable source?] As indicated above, Cytochrome P450 reductase (POR ... Proteins and Proteomics. 1814 (1): 210-22. doi:10.1016/j.bbapap.2010.09.009. PMID 20869469. Moran, J. H.; Weise, R; Schnellmann ...
Squalene oxidation activates NF-κB (a protein complex) and consequently increases IL-1α levels. Additionally, squalene ... peroxisome proliferator-activated receptor modulators, and inhibitors of the stearoyl-CoA desaturase-1 enzyme are also a focus ... LTB4 promotes skin inflammation by acting on the peroxisome proliferator-activated receptor alpha (PPARα) protein. PPARα ... Once the light activates the sensitizing substance, this generates free radicals and reactive oxygen species in the skin, which ...
Linker of activated T cells, Lymphocyte cytosolic protein 2, MAP2, MAP3K1 MAP4K1, MED28, MST1R, MUC1, Mitogen-activated protein ... "Direct binding of the signal-transducing adaptor Grb2 facilitates down-regulation of the cyclin-dependent kinase inhibitor ... "Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth ... the guanine nucleotide exchange protein Sos and a 75-kDa protein that is a substrate for T cell antigen receptor-activated ...
White blood cells are activated by upregulation of integrin avidity, the lipoxygenase pathway and arachidonic acid metabolism. ... C5aR is a member of the G-protein-coupled receptor superfamily of proteins, predicted to have seven transmembrane helical ... The inhibitor of C5a that can block its effects would be helpful in medical applications. Another candidate is PMX53 or PMX205 ... C5a is a protein fragment released from cleavage of complement component C5 by protease C5-convertase into C5a and C5b ...
Kelavkar, U. P; Cohen, C (2004). "15-lipoxygenase-1 expression upregulates and activates insulin-like growth factor-1 receptor ... HODE directly activate human (but not mouse) GPR132 (G protein coupled receptor 132, also termed G2A) in Chinese hamster ovary ... Ruparel, Shivani; Green, Dustin; Chen, Paul; Hargreaves, Kenneth M (2012). "The Cytochrome P450 Inhibitor, Ketoconazole, ... 12-lipoxygenase, and 15-lipoxygenase-2, and selected metabolites of the latter lipoxygenases show no such association. ...
"Probing conformational changes in lipoxygenases upon membrane binding: Fine-tuning by the active site inhibitor ETYA". Biochim ... 2013). "Dietary fish oil and DHA down-regulate antigen-activated CD4+ T-cells while promoting the formation of liquid-ordered ... 1986). "Estimation of the polarity of the protein interior by optical spectroscopy". Nature. 319 (6048): 70-73. Bibcode: ... 18 (5): 591-598. doi:10.1016/j.semcdb.2007.07.011. PMID 17728161. Bagatolli, L. A. (2006). "To see or not to see: lateral ...
13(S)-HpODE, and 13(S)-HODE directly activate human (but not mouse) GPR132 (G protein coupled receptor 132, also termed G2A) in ... 12-lipoxygenase, and 15-lipoxygenase-2, and selected metabolites of the latter lipoxygenases show no such association.[66][67][ ... all of which are inhibitors of cultured human prostate cancer cell proliferation.[81][82][83] ... 15-Lipoxygenase 1[edit]. 15-lipoxygenase 1 (ALOX15), while best known for converting the 20 carbon polyunsaturated fatty acid, ...
... p120 gtpase activating protein MeSH D12.776.402.300.700.500 - ras-GRF1 MeSH D12.776.402.300.700.700 - son of sevenless proteins ... wnt1 protein MeSH D12.776.624.664.700.978 - wnt2 protein MeSH D12.776.624.776.355.100 - cyclin-dependent kinase inhibitor p15 ... lipoxygenase MeSH D12.776.556.579.374.450.025 - arachidonate lipoxygenases MeSH D12.776.556.579.374.450.025.020 - arachidonate ... groel protein MeSH D12.776.602.500.500.100 - fusion proteins, bcr-abl MeSH D12.776.602.500.500.320 - fusion proteins, gag-onc ...
Squalene oxidation activates NF-κB (a protein complex) and consequently increases IL-1α levels.[45] Additionally, squalene ... peroxisome proliferator-activated receptor modulators, and inhibitors of the stearoyl-CoA desaturase-1 enzyme are also a focus ... LTB4 promotes skin inflammation by acting on the peroxisome proliferator-activated receptor alpha (PPARα) protein.[45] PPARα ... C. acnes' ability to bind and activate a class of immune system receptors known as toll-like receptors (TLRs), especially TLR2 ...
is modified to include binding of the inhibitor to the free enzyme:. EI. +. S. ⇌. k. 3. k. −. 3. E. +. S. +. I. ⇌. k. −. 1. k. ... MPTP is able to cross the blood brain barrier and enter acidic lysosomes.[13] MPTP is biologically activated by MAO-B, an ... The active site is a region on an enzyme which a particular protein or substrate can bind to. The active site will only allow ... is the inhibitor concentration.. V. max. {\displaystyle V_{\max }}. remains the same because the presence of the inhibitor can ...
Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... Withaferin A potent inhibitor of angiogenesis. References[edit]. *^ Hannink M, Donoghue DJ (1989). "Structure and function of ... There are five different isoforms of PDGF that activate cellular response through two different receptors. Known ligands ... "12/15-Lipoxygenase Contributes to Platelet-derived Growth Factor-induced Activation of Signal Transducer and Activator of ...
"Expression of X-linked inhibitor of apoptosis protein in human prostate cancer specimens with and without neo-adjuvant hormonal ... AR, an androgen-activated transcription factor, belongs to the steroid nuclear receptor family. Development of the prostate is ... checkpoint inhibitor ipilimumab, CYP17 inhibitor galeterone (TOK-001), and immunotherapy PROSTVAC.[185] ... As of 2016[update] PARP inhibitor olaparib has shown promise in clinical trials for CRPC.[185] Also in trials for CRPC are : ...
... and/or 271 by Mitogen-activated protein kinases, S6 kinase, protein kinase A (PKA), protein kinase C, Cdc2, and/or a Ca2+/ ... To date, however, neither LTB4 synthesis inhibitors (i.e. blockers of ALOX5 or LTA4 hydrolase) nor inhibitors of LTB4 receptors ... ALOX5 binds with the F actin-binding protein, coactin-like protein. Based on in vitro studies, this protein binding serves to ... This chemotactic factor stimulation concurrently causes the activation of mitogen-activated protein kinases (MAPK) which in ...
In 2012, salicylic acid was found to activate AMP-activated protein kinase, which has been suggested as a possible explanation ... Factor Xa inhibitors. (with some II inhibition). Heparin group/. glycosaminoglycans/. (bind antithrombin). *Low molecular ... It is proposed that this aspirin-triggered transition of COX-2 from cyclooxygenase to lipoxygenase activity and the ... "The ancient drug salicylate directly activates AMP-activated protein kinase". Science. 336 (6083): 918-22. Bibcode:2012Sci... ...
CysLTR2, similar to CysLTR1, is a G protein-coupled receptor that links to and when bound to its CysLT ligands activates the Gq ... CysLTR2 inhibitors[edit]. There are as yet no selective inhibitors of CysLTR2 that are in clinical use (see Clinical ... Haeggström JZ, Funk CD (October 2011). "Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease". ... protein binding. • G-protein coupled peptide receptor activity. • signal transducer activity. • G-protein coupled receptor ...
... mitogen-activated-protein kinase-activating protein kinase) has a preference for Ser40, but also phosphorylates Ser19 about ... Older examples of inhibitors mentioned in the literature include oudenone[45] and aquayamycin.[46] ... Tyrosine hydroxylase is activated by phosphorylation dependent binding to 14-3-3 proteins.[34] Since the 14-3-3 proteins also ... protein binding. • amino acid binding. • monooxygenase activity. • protein domain specific binding. Cellular component. • ...
Leukotriene A4 hydrolase, also known as LTA4H is a human gene.[1][2][3] The protein encoded by this gene is a bifunctional ... Crystallographic structure of LTA4H (rainbow colored N-terminus = blue, C-terminus = red) complexed with the protease inhibitor ... Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase". J. Biol. ... 5,6-epoxyicosa-7,9,11,14-tetraenoate hydrolase. Other names in common use include LTA4 hydrolase, LTA4H, and leukotriene A4 ...
COX-2 up-regulation has also been linked to the phosphorylation and activation of the E3 ubiquitin ligase HDM2, a protein that ... "Calcium-activated endoplasmic reticulum stress as a major component of tumor cell death induced by 2,5-dimethyl-celecoxib, a ... of NSAID expenditures were for COX-2 inhibitors. Over the period of the study, COX-2 inhibitors rose from 10.03% of total ... "COX-2 Inhibitors and Cancer". Fact Sheet. United States National Cancer Institute. Archived from the original on May 9, 2008.. ...
competitive nonselective phosphodiesterase inhibitor,[19] which raises intracellular cAMP, activates PKA, inhibits TNF-alpha[20 ... The protein binding is 40%. The volume of distribution may increase in neonates and those suffering from cirrhosis or ... theophylline has been shown to directly activate HDAC2.[25] (Corticosteroids switch off the inflammatory response by blocking ... 108 (5): 671-80. doi:10.1067/mai.2001.119555. PMID 11692087.. *^ Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R (2008 ...
... which binds to ribonucleases in one of the tightest known protein-protein interactions.[1] Natural enzyme inhibitors can also ... Examples of slow-binding inhibitors include some important drugs, such methotrexate,[30] allopurinol,[31] and the activated ... Reversible inhibitors[edit]. Types of reversible inhibitors[edit]. Reversible inhibitors attach to enzymes with non-covalent ... fraction of the enzyme population bound by inhibitor [. I. ]. [. I. ]. +. K. i. {\displaystyle {\cfrac {{\ce {[I]}}}{[{{\ce {I ...
ARA also activates syntaxin-3 (STX-3), a protein involved in the growth and repair of neurons.[25] ... The enzymes 15-lipoxygenase-1 (ALOX15 and 15-lipoxygenase-2 (ALOX15B metabolize arachidonic acid to 15- ... inhibitors). COX. (PTGS). *Salicylic acids: Aloxiprin. *Aspirin (acetylsalicylic acid). *Benorilate (benorylate). *Carbasalate ... It also helps protect the brain from oxidative stress by activating peroxisome proliferator-activated receptor gamma.[24] ...
"Expression of X-linked inhibitor of apoptosis protein in human prostate cancer specimens with and without neo-adjuvant hormonal ... AR, an androgen-activated transcription factor, belongs to the steroid nuclear receptor family. Development of the prostate is ... checkpoint inhibitor ipilimumab, CYP17 inhibitor galeterone (TOK-001), and immunotherapy PROSTVAC.[183] ... As of 2016[update] PARP inhibitor olaparib has shown promise in clinical trials for CRPC.[183] Also in trials for CRPC are : ...
A trypsin inhibitor (TI) is a protein and a type of serine protease inhibitor (serpin) that reduces the biological activity of ... However, experiments have been done concerning animals who consume activate trypsin inhibitor and they consistently have ... Also known as BPTI (basic pancreatic trypsin inhibitor) and Kunitz inhibitor. Best-known pancreatic inhibitor. Inhibits several ... It competes with proteins to bind to trypsin and therefore renders it unavailable to bind with proteins for the digestion ...
The proteins are activated by adding a phosphate group to the protein (phosphorylation), a step that TKIs inhibit. TKIs are ... Protein kinase inhibitor. References[edit]. *^ Yaish P, Gazit A, Gilon C, Levitzki A (1988). "Blocking of EGF-dependent cell ... RET inhibitors: Vandetanib (also VEGFR and EGFR). Entrectinib (ALK, ROS1, NTRK). c-MET inhibitor: Cabozantinib (also VEGFR2). ... "ATP-competitive inhibitors block protein kinase recruitment to the Hsp90-Cdc37 system". Nture Chem Biol. 9 (5): 307-312. doi: ...
The bradykinin peptide is well known to promote a cough reaction associated with ACE inhibitor medications prescribed for ... Griffiths, T. W. (2010). "Effects of trenbolone acetate and resorcylic acid lactone on protein metabolism and growth in steers ... However, trenbolone acetate's androgenic effect activates a variety of lipid-like active compounds which are called ... and lipoxygenases (LOX) (also known as: EC 1.13.11.34, EC 1.13.11.33, etc.).[22] Vasoconstriction of the muscular wall of the ...
The activated glucocorticoid receptor-glucocorticoid complex up-regulates the expression of anti-inflammatory proteins in the ... nucleus (a process known as transactivation) and represses the expression of proinflammatory proteins in the cytosol by ... 5/h10-11,13,16,19-21,31H,6-9,12,14-15H2,1-5H3/t16-,19-,20-,21-,25-,26-,27-,28-/m0/s1 Y ...
protein homodimerization activity. • dioxygenase activity. • protein binding. • oxidoreductase activity, acting on single ... Non-substrate FAs can potentiate or attenuate PTGS (COX) inhibitors depending on the fatty acid and whether the inhibitor binds ... arachidonate 15-lipoxygenase activity. • metal ion binding. • heme binding. • enzyme binding. • oxidoreductase activity. • ... Allosteric subunit binds a non-substrate, activating FA (e.g., palmitic acid). The allosteric subunit with bound fatty acid ...
COX, the lipoxygenases, and the phospholipases are tightly controlled-there are at least eight proteins activated to coordinate ... Clinical trial number NCT00847899 for "Evaluation of Soluble Epoxide Hydrolase (s-EH) Inhibitor in Patients With Mild to ... The enzymes 15-lipoxygenase-1 (15-LO-1 or ALOX15) and 15-lipoxygenase-2 (15-LO-2, ALOX15B) metabolize arachidonic acid to the S ... Other reactions of lipoxygenases generate cellular damage; murine models implicate 15-lipoxygenase in the pathogenesis of ...
"Expression of X-linked inhibitor of apoptosis protein in human prostate cancer specimens with and without neo-adjuvant hormonal ... and is activated manually by the patient through a switch implanted in the scrotum. The latter is considered the gold standard ... Also in trials for CRPC are : checkpoint inhibitor ipilimumab, CYP17 inhibitor galeterone (TOK-001), and immunotherapy PROSTVAC ... Transport protein ZIP1 is responsible for the transport of zinc into prostate cells. One of zinc's important roles is to change ...
One or both of these compounds stimulates cells by binding with and activating two G protein-coupled receptors, GPR31 and the ... ALOX15 (also termed arachidonate 15-lipoxygenase, 15-lipoxygenase-1, 15-LO-1, 15-LOX-1) is, like other lipoxygenases, a seminal ... an inhibitor of human platelet aggregation (see Dihydroxy-E,Z,E-PUFA). 5(S),15(S)-dihydroxy-6Z,8E,llE,13Z-eicosatetraenoic acid ... 15-lipoxygenase-2, 15-LOX-2, 15-LO-2, arachidonate 15-lipoxygenase type II, arachidonate 15-lipoxygenase, second type, and ...
The ability of various inhibitors of lipoxygenase (LOX) enzymes and 5-lipoxygenase-activating protein (FLAP) to induce ... This conclusion was further supported by the fact that a more specific FLAP inhibitor, MK591, induced only minimal apoptosis in ... MK886 induced apoptosis in WSU cells, a human chronic lymphocytic leukaemia cell line that lacks FLAP protein and mRNA, ... Furthermore, the concentration of MK886, a FLAP inhibitor, required to induce apoptosis is ≈ 100-fold more than that required ...
... recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, ... BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and ... Proteasome Inhibitors(28). *Protein Arginine Deiminase (PAD) Inhibitors(7). *Protein Kinase Inhibitors(863)*Protein Kinase ... Ubiquitin Activating Enzyme E1 Inhibitor(1). *Ubiquitin Ligase (E3) Inhibitors(9). *Ubiquitin Proteasome Pathway Inhibitors(44) ...
Cells were lysed in presence of protease inhibitors, and the lysate was subjected to immunoprecipitation with an affinity- ... To study the roles of the 5LO accessory proteins coactosin-like protein (CLP) and 5LO-activating protein (FLAP), we knocked ... Cellular formation of LTs from endogenous AA depends on the small membrane protein 5LO-activating protein (FLAP) (4). FLAP has ... MAP kinase pathways can activate 5LO during cell stress (7), whereas phosphorylation by protein kinase A inhibits cellular 5LO ...
Inhibitors Overview. B-Cell Activating Factor (BAFF) Inhibitors Disease Associated. B-Cell Activating Factor (BAFF) Inhibitors ... B-Cell Activating Factor (BAFF) Inhibitors Assessment by Stage and Molecule Type. B-Cell Activating Factor (BAFF) Inhibitors ... B-Cell Activating Factor (BAFF) Inhibitors Phase II Products. Comparative Analysis. B-Cell Activating Factor (BAFF) Inhibitors ... B-Cell Activating Factor (BAFF) Inhibitors Assessment by Route of Administration. B-Cell Activating Factor (BAFF) Inhibitors ...
Until recently, it has been impossible to grow large protein crystals of endothiapepsin with any gem-diol inhibitor that are ... thermophilus leads to robust crystallization of the protein in space group P41212; crystals of these mutant proteins show X-ray ... The crystal structure of the minimized α/β-hydrolase fold protein encoded by the gene TTHA1544 from T. thermophilus HB8 has ... In this study, the Korean pine (Pinus koraiensis) vicilin-type 7S seed storage protein was isolated from defatted pine-nut ...
This protein is involved in the production of cysteinyl leukotrienes which are involved in inflammation, and AM-679 has anti- ... AM-679 is a drug which acts as a selective inhibitor of 5-Lipoxygenase-activating protein (FLAP). ... a potent FLAP inhibitor". Bioorganic & Medicinal Chemistry Letters. 20 (1): 213-7. doi:10.1016/j.bmcl.2009.10.131. PMID ... Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H- ...
Lipoxygenase and cyclooxygenase inhibitors reveal a complementary role of arachidonic acid derivatives ... ... 1.62 pg/mg protein), suggesting the presence of soluble epoxide hydrolase (sEH). The addition of an sEH inhibitor to MSC ... a peroxisome proliferator-activated receptor gamma agonist. Typically, studies use taurocholic acid (TCA) as a model substrate ... The bile salt export pump (BSEP, ABCB11) is the major transporter protein for the excretion of bile salts into bile. Here we ...
Use of prescription or non-prescription drugs, including CYP3A4 inhibitors and inducers, vitamins, herbal and dietary ... GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor. Drug: GSK2190915 GSK2190915 is a high ... 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). ... this far exceeds the 5 half lives after administration of the last dose). ...
Enantioselective Photoreduction of Activated Ketones and Ketimines * Full Text * HTML * PDF (105 kb) ... Inhibitor * Full Text * HTML ... Synthesis of a 5-Lipoxygenase Activating Protein (FLAP) ... trans-Selective Alkynylboration of Alkynes to 4-Alkynyl-1,2-oxaborol-2(5H)-ols * Full Text ...
Potent 5-lipoxygenase activating protein inhibitor (FLAP) (IC50 = 44 nM). Inhibits leukotriene biosynthesis (IC50 = 2.5 nM) in ... Proteins and Peptides. By product type. Proteomics tools. Agonists, activators, antagonists and inhibitors. Cell lines and ... Tao T et al. Role of adiponectin/peroxisome proliferator-activated receptor alpha signaling in human chorionic gonadotropin- ... Potent 5-lipoxygenase activating protein inhibitor (FLAP) (IC50 = 44 nM). Inhibits leukotriene biosynthesis (IC50 = 2.5 nM) in ...
Lipoxygenase (5‐LOX) catalyses two steps in thebiosynthesis of leukotrienes (LTs), lipid mediators of inflammation derived from ... Lipoxygenaseactivating protein inhibitors for inflammatory diseases. Trends in Pharmacological Sciences 29: 72-78. ... lipoxygenaseactivating protein. Science 317: 510-512. Flamand N, Luo M, Peters‐Golden M et al. (2009) Phosphorylation of ... lipoxygenaseactivating protein homodimer in human neutrophils: evidence for a role in leukotriene biosynthesis. Biochemical ...
"Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein". Science. 317 (5837): 510-2. Bibcode:2007Sci... ... How FLAP activates 5-lipooxygenase is not completely understood, but there is a physical interaction between the two. FLAP ... It is an integral protein within the nuclear membrane. FLAP is necessary in synthesis of leukotriene, which are lipid mediators ... Leukotrienes, which need the FLAP protein to be made, have an established pathological role in allergic and respiratory ...
LTB4 is able to recruit and activate inflammatory cells, which in turn can cause tissue damage and disease. Elevated levels of ... This relative decrease in potency could partially be ascribed to protein binding because the IC50 value obtained when the ... LTA4H inhibitors specifically block the production of LTB4 from LTA4, without affecting the biosynthesis of lipoxins, which are ... Penning TD (2001) Inhibitors of leukotriene A4 (LTA4) hydrolase as potential anti-inflammatory agents. Curr Pharm Des 7: 163- ...
S100 calcium binding protein B as a biomarker of delirium duration in the intensive care unit - an exploratory analysis Khan BA ... Effects of proton pump inhibitors and electrolyte disturbances on arrhythmias El-Charabaty E, Saifan C, Abdallah M, Naboush A, ... This site is owned and operated by Informa PLC ( "Informa") whose registered office is 5 Howick Place, London SW1P 1WG. ... Inhibition of the early asthmatic response to inhaled allergen by the 5-lipoxygenase activating protein inhibitor GSK2190915: a ...
Five-lipoxygenase activating protein (FLAP) inhibitors including 2190914 (AM-103) (Lorrain et al., 2009; Bain et al., 2010) and ... Data on the effectiveness of LTRA, phosphodiesterase inhibitors, mast cell tryptase inhibitors, and peroxisome proliferator- ... Sampson, A. P. (2009). FLAP inhibitors for the treatment of inflammatory diseases. Curr. Opin. Investig. Drugs 10, 1163-1172. ... Several inflammatory biomarkers, including eosinophil-derived proteins, NO-derived metabolites, eicosanoids, cytokines, and ...
Inhibitor of 5-lipoxygenase-activating protein (FLAP). Cited in 10 publications. ... protein, FLAP, PPARα, PPARalpha, antagonists, inhibitors, inhibits, Oxygenases, Oxidases, leukotrienes, eicosanoids, ... Kehrer et al (2001) Inhibition of peroxisome-proliferator-activated receptor (PPAR)α by MK886. Biochem.J. 356 899 PMID: ... Lipoxygenase, Receptors, Leukotriene, and, Related, 1311, Tocris Bioscience ...
Inhaled p38alpha mitogen-activated protein kinase antisense oligonucleotide attenuates asthma in mice. Am J Respir Crit Care ... Corticosteroids Bronchodilator Kinase inhibitors ER stress inhibitors Mitochondria-targeting antioxidants PDE4 inhibitors Type ... p38 mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid- ... A novel dithiol amide CB3 attenuates allergic airway disease through negative regulation of p38 mitogen-activated protein ...
FLAP inhibitors and the novel-type 5-LO inhibitors licofelone and sulindac sulfide exhibited higher potencies in human blood ... Following platelet-activating factor-induced shock, MK886 increased survival exclusively in female mice, and this effect was ... Lower doses of the FLAP inhibitor MK886 were required to reduce LTB4 levels in exudates of female versus male mice and rats. ... Androgen-mediated sex bias impairs efficiency of leukotriene biosynthesis inhibitors in males. J Clin Invest. 2017;127(8):3167- ...
Dietary Protein and the Regulation of Long-Bone and Muscle Growth in the Rat Clin Sci (Lond) (August, 1994) ... inhibitor, MK886, induces apoptosis independently of FLAP Biochem J (May, 1999) ...
It cannot be ruled out that the cellular effect of candesartan cilexetil may be partly due to its effect on other proteins in ... as well as adducts induced by activated polycyclic aromatic hydrocarbons such as benzo[a]pyrene diolepoxide [7]-[14]. ... The cells were treated with (1) inhibitor alone for 6 h or (2) UV alone or (3) inhibitor alone for 6 h followed by UV ... As shown in Figure 6, the inhibitor potentiated the cytotoxicity of UV at higher UV doses (4.5 and 7.5 J/m2). The assay was ...
... activating protein inhibitor, on exercise-induced bronchoconstriction pp. 126-133(8) Authors: Kent, Sandra E .; Bentley, Jane H ...
Protein Coding), Arachidonate 5-Lipoxygenase Activating Protein, including: function, proteins, disorders, pathways, orthologs ... and 12-Lipoxygenase inhibitor. 491-67-8. BAY-X 1005. Orally active 5-lipoxygenase activating protein (FLAP) inhibitor. 128253- ... Membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG) * Five-lipoxygenase activating protein signature ... This protein localizes to the plasma membrane. Inhibitors of its function impede translocation of 5-lipoxygenase from the ...
Role of p38 mitogen-activated protein kinase in linking stearoyl-CoA desaturase-1 activity with endoplasmic reticulum ... Cyclooxygenase-2 inhibitors. 1,5-diarylpyrrol-3-acetic esters with enhanced inhibitory activity toward cyclooxygenase-2 and ... Can Small Chemical Modifications of Natural Pan-inhibitors Modulate the Biological Selectivity? The Case of Curcumin Prenylated ... Indirubin core structure of glycogen synthase kinase-3 inhibitors as novel chemotype for intervention with 5-lipoxygenase. ...
mitogen-activated protein (MAP) kinase inhibitors. -mastat (see -stat). matrix metalloproteinase inhibitors. ... antibacterials, streptogramins, protein synthesis inhibitors, pristinamycin derivatives. -profen. anti-inflammatory agents, ... peroxisome proliferator activating receptor-γ (PPAR-γ) agonists. -glitazone (see gli). peroxisome proliferator activating ... angiotensin-converting enzyme inhibitors. -prim. antibacterials, dihydrofolate reductase (DHFR) inhibitors, trimethoprim ...
... articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated ... H. J. Hussey and M. J. Tisdale, "Inhibition of tumour growth by lipoxygenase inhibitors," British Journal of Cancer, vol. 74, ... or X induces interleukin-8 and cyclooxygenase-2 gene and protein expression through peroxisome proliferator-activated receptors ... I. Avis, S. H. Hong, A. Martinez et al., "Five-lipoxygenase inhibitors can mediate apoptosis in human breast cancer cell lines ...
Role of heat shock proteins in the pathogenesis of cystic fibrosis arthritis. (1 December, 1997) Free M R al-Shamma, C McSharry ... Enhancement of leukotriene B4 release in stimulated asthmatic neutrophils by platelet activating factor. (1 December, 1997) ... Effect of a novel 5-lipoxygenase activating protein inhibitor, BAYx 1005, on asthma induced by cold dry air. (1 December, 1997 ...
Tuberculosis in National Health Service hospital staff in the west Midlands region of England, 1992-5. A Hill, A Burge, C ... Effect of a novel 5-lipoxygenase activating protein inhibitor, BAYx 1005, on asthma induced by cold dry air. A R Fischer, M A ...
GTPase-activating protein, Gcs1 Kanamarlapudi VENKATESWARLU, Paru B. OATEY, Jeremy M. TAVARÉ, Trevor R. JACKSON, Peter J. ... inhibitor, MK886, induces apoptosis independently of FLAP Kaushik DATTA, Shyam S. BISWAL, James P. KEHRER ... Identification of peroxisomal proteins by using M13 phage protein VI phage display: molecular evidence that mammalian ... Stable expression of protective protein/cathepsin A-green fluorescent protein fusion genes in a fibroblastic cell line from a ...
... inhibitors in respiratory and cardiovascular disease.. Amira combines the rigor of a big pharmaceutical company with the ... 5. Anti-Fibrotic Data from Amira Pharmaceuticals LPA1 Receptor Antagonist Program Published in the British Journal of ... Amira has a partnership with GlaxoSmithKline for the development of FLAP (5-lipoxygenase-activating protein) ...
IL-5 and IL-13. Neutrophilic bronchitis represents a non-T2 driven disease, which is generally a predictor of response to ... Protein microarray data of induced sputum were stratified by sputum cell differential (eosinophilic: ≥2% eos and ,40% neuts; ... Effects of a FLAP inhibitor, GSK2190915, in asthmatics with high sputum neutrophils. Pulm Pharmacol Ther (2014) 27(1):62-9. doi ... It should be acknowledged that the mere presence of a particular gene, protein or a cell do not necessarily make them a ...
  • The ability of various inhibitors of lipoxygenase (LOX) enzymes and 5-lipoxygenase-activating protein (FLAP) to induce apoptosis has implicated these pathways in the mechanism(s) of this form of cell death. (portlandpress.com)
  • Although FLAP plays an important role in 5-LOX activity, this protein is found at high levels in some cells lacking LOX, suggesting it might mediate other effects. (portlandpress.com)
  • Furthermore, the concentration of MK886, a FLAP inhibitor, required to induce apoptosis is ≈ 100-fold more than that required to inhibit LOX, and this compound remains effective in cells lacking LOX. (portlandpress.com)
  • MK886 induced apoptosis in WSU cells, a human chronic lymphocytic leukaemia cell line that lacks FLAP protein and mRNA, suggesting that this agent is acting independently of FLAP. (portlandpress.com)
  • This conclusion was further supported by the fact that a more specific FLAP inhibitor, MK591, induced only minimal apoptosis in FL5.12 cells, a murine prolymphoid cell line containing FLAP. (portlandpress.com)
  • To study the roles of the 5LO accessory proteins coactosin-like protein (CLP) and 5LO-activating protein (FLAP), we knocked down these proteins in human monocytic cells. (pnas.org)
  • Two accessory proteins, coactosin-like protein (CLP) and 5-lipoxygenase-activating protein (FLAP), can support 5LO activity. (pnas.org)
  • To study the roles of CLP and FLAP, we knocked down these proteins in the human monocytic cell line Mono Mac 6 (MM6). (pnas.org)
  • AM-679 is a drug which acts as a selective inhibitor of 5-Lipoxygenase-activating protein (FLAP). (wikipedia.org)
  • Potent 5-lipoxygenase activating protein inhibitor (FLAP) (IC 50 = 44 nM). (abcam.com)
  • 5‐LOX interacts with various proteins such as FLAP, CLP and Dicer. (els.net)
  • Upon cell stimulation soluble 5‐LOX binds Ca 2+ and may become phosphorylated, and then translocates to the nuclear envelope where it binds to the outer or inner nuclear membrane via Ca 2+ close to membrane‐integrated FLAP . (els.net)
  • AA liberated by cPLA 2 is transferred via FLAP to 5‐LOX producing LTA 4 that is converted by LTC 4 S (cytosolic side) or LTA 4 H (intranuclear) to LTC 4 or LTB 4 , respectively. (els.net)
  • Arachidonate 5-lipoxygenase-activating protein also known as 5-lipoxygenase activating protein, or FLAP, is a protein that in humans is encoded by the ALOX5AP gene. (wikipedia.org)
  • FLAP is necessary for the activation of 5-lipoxygenase and therefore for the production of leukotrienes, 5-hydroxyeicosatetraenoic acid, 5-oxo-eicosatetraenoic acid, and specialized pro-resolving mediators of the lipoxin and resolvin classes. (wikipedia.org)
  • FLAP functions as a membrane anchor for 5-lipooxygenase and as an amine acid-bind protein. (wikipedia.org)
  • How FLAP activates 5-lipooxygenase is not completely understood, but there is a physical interaction between the two. (wikipedia.org)
  • Leukotrienes, which need the FLAP protein to be made, have an established pathological role in allergic and respiratory diseases. (wikipedia.org)
  • Potent inhibitor of 5-lipoxygenase-activating protein (FLAP) (IC 50 = 30 nM for inhibition of [ 125 I]-L-691,678 photoaffinity labelling). (tocris.com)
  • Proinflammatory leukotrienes (LTs) are produced by 5-lipoxygenase (5-LO) aided by 5-LO-activating protein (FLAP). (jci.org)
  • We found that androgens cause these sex differences by impeding the LT-biosynthetic 5-LO/FLAP complex assembly. (jci.org)
  • Lower doses of the FLAP inhibitor MK886 were required to reduce LTB4 levels in exudates of female versus male mice and rats. (jci.org)
  • FLAP inhibitors and the novel-type 5-LO inhibitors licofelone and sulindac sulfide exhibited higher potencies in human blood from females, and bioactive 5-LO/FLAP complexes were formed in female, but not male, human and murine leukocytes. (jci.org)
  • Amira has a partnership with GlaxoSmithKline for the development of FLAP (5-lipoxygenase-activating protein) inhibitors in respiratory and cardiovascular disease. (bio-medicine.org)
  • The expression of 5-lipoxygenase activating protein (FLAP) in murine hematopoietic FL5.12 cells that are transfected to overexpress bcl-x L is less than in control cells. (elsevier.com)
  • A proteolytic mechanism was explored by examining the effect of the general caspase inhibitor Boc-D-FMK, and the non-caspase protease inhibitors phenylmethylsulfonyl fluoride (PMSF), pepstatin and leupeptin, on the loss of FLAP in bcl-x L overexpressing cells subsequent to IL-3 withdrawal. (elsevier.com)
  • All inhibitors provided some protection from the loss of FLAP, with PMSF being the most effective, actually increasing FLAP levels above those seen in untreated cells. (elsevier.com)
  • Biswal, SS , Datta, K & Kehrer, JP 2001, ' Association between bcl-x L and 5-lipoxygenase activating protein (FLAP) levels in IL-3-dependent FL5.12 cells ', Toxicology , vol. 160, no. 1-3, pp. 97-103. (elsevier.com)
  • MK-886 is an inhibitor of leukotriene biosynthesis , inhibiting 5-lipoxygenase-activating protein (FLAP) . (selleckchem.com)
  • MK886, a strong proapoptotic agent, is an inhibitor of 5-lipoxygenase (LOX) through binding to the 5-LOX-activating protein (FLAP). (biochemj.org)
  • Induction could also be achieved with another FLAP inhibitor, MK591. (biochemj.org)
  • The initial catalytic step in the formation of leukotrienes is catalyzed by 5-lipoxygenase (5-LOX) in conjunction with its activating partner protein FLAP. (sciencemag.org)
  • Cells showing positive antibody binding to 5-LO, FLAP (5-lipoxygenase activating protein), and leukotriene A 4 hydrolase were also present in the coronary arteries and had a similar distribution to macrophages. (ahajournals.org)
  • 5 6 The synthetic pathway for leukotrienes is initiated by the release of arachidonic acid from the cell membrane by phospholipase A 2 , followed by its conversion to leukotriene A 4 (LTA 4 ) by the enzyme 5-LO and its activating protein, FLAP. (ahajournals.org)
  • DG031 is a small-molecule inhibitor of the 5-lipoxygenase activating protein, or FLAP, encoded by a gene that deCODE has linked to significantly increased risk of heart attack. (decode.com)
  • Rheumatoid arthritis synovial fibroblasts were treated with the cyclooxygenase inhibitor naproxen, the 5-LO inhibitor BWA4C and the 5-lipoxygenase-activating protein (FLAP) inhibitor MK886, and consecutive changes in CXCL10 protein levels measured. (uzh.ch)
  • Whereas inhibition of the cyclooxygenase pathway or the FLAP protein showed no effect, blockade of 5-LO significantly downregulated CXCL10 protein levels. (uzh.ch)
  • The 5-lipoxygenase activating protein (FLAP) inhibitors displace arachidonic acid from its binding site on the FLAP molecule and prevent this substrate from being presented to 5-lipoxygenase. (nps.org.au)
  • FLAP inhibitors for the treatment of inflammatory diseases. (semanticscholar.org)
  • Quiflapon sodium (MK-591 sodium) is a selective and specific 5-Lipoxygenase-activating protein ( FLAP ) inhibitor. (medchemexpress.com)
  • 5-Lipoxygenase-activating protein (FLAP) and microsomal prostaglandin E2 synthase-1 (mPGES-1) are important targets for new generation nonsteroidal anti-inflammatory drugs, and interfering with both targets in the AA pathway promises higher efficacy and better safety profile as opposed to single target drugs. (wixsite.com)
  • The three successive research projects (#108S210, #112S596, #218S555) are funded by The Scientific and Technological Research Council of Turkey (TUBITAK) on the development of novel FLAP and mPGES-1 inhibitors, and carried out in collaboration with our colleagues Prof. Oliver Werz (University of Jena) and Prof. Antonio Macchiarulo (University of Perugia). (wixsite.com)
  • In summary, we discovered selective FLAP (BRP-7) and selective mPGES-1 (BRP-151) inhibitors as well as multi-target inhibitors that potently and dually interfere with FLAP and mPGES-1 in LT and PGE2 biosynthesis, namely BRP-187 and BRP-201. (wixsite.com)
  • THE 5-LOX interface involving the four cysteines 159, 300, 416 and 418 is important for the translocation to the nuclear membrane and the colocalization with FLAP. (nih.gov)
  • AZD-5718 is an orally available small molecule, 5-lipoxygenase activating protein (FLAP) inhibitor. (probechem.com)
  • Comparative Molecular Field Analysis (CoMFA) and molecular docking studies were carried out on a series of substituted 2,2-bisaryl-bicycloheptanes FLAP inhibitors. (certara.com)
  • The analyses may be used to design more potent FLAP inhibitors and predict their activities prior to synthesis. (certara.com)
  • MK-886 (L 663536) is a potent, cell-permeable and orally active FLAP ( IC 50 of 30 nM) and leukotriene biosynthesis ( IC 50 s of 3 nM and 1.1 μM in intact leukocytes and human whole blood, respectively) inhibitor. (medchemexpress.com)
  • AM-803) is a potent and orally bioavailable 5-lipoxygenase-activating protein ( FLAP ) inhibitor with a potency of 2.9 nM in FLAP binding, an IC 50 of 76 nM for inhibition of LTB4 in human blood. (medchemexpress.com)
  • The present invention provides processes useful for preparing 5-lipoxygenase activating protein (FLAP) inhibitors and their intermediates. (patentsencyclopedia.com)
  • [0001] Described herein are processes useful for preparing 5-lipoxygenase activating protein (FLAP) inhibitors and their intermediates. (patentsencyclopedia.com)
  • Leukotrienes (LTs) are a class of mediators derived from arachidonic acid by the initiating activity of 5-lipoxygenase and 5-lipoxygenase-activating protein (FLAP). (jci.org)
  • [3] [4] drugs such as MK-886 that block the 5-lipoxygenase activating protein (FLAP) inhibit functioning of the 5-lipoxygenase enzyme and may help in treating atherosclerosis . (wikipedia.org)
  • the enzymes 5-lipoxygenase (5-LO, ALOX5) with its activating protein, FLAP (ALOX5AP), LTA4 hydrolase and LTC4 synthase, as well as the receptors for leukotriene B4 (BLT1 and BLT2) and cysteinyl-leukotrienes (CysLT1 and CysLT2), respectively. (eurekaselect.com)
  • When such cells are activated, arachidonic acid is liberated from cell membrane phospholipids by phospholipase A2and donated by the 5-lipoxygenase-activating protein FLAP to 5-lipoxygenase. (arragons-triathlon.club)
  • DG031 is designed to inhibit the FLAP, or 5-lipoxygenase activating protein, which regulates the synthesis of leukotrienes. (decode.com)
  • 5-Lipoxygenase activating protein (FLAP) plays a critical role in the metabolism of arachidonic acid to leukotriene A4, the precursor to the potent pro-inflammatory mediators leukotriene B4 and leukotriene C4 Studies with small molecule inhibitors of FLAP have led to the discovery of a drug binding pocket on the protein surface, and several pharmaceutical companies have developed compounds and performed clinical trials. (faintpower.cf)
  • 5-Lipoxygenase (5LO) is a key enzyme in biosynthesis of leukotrienes (LTs), lipid mediators of inflammation. (pnas.org)
  • This protein is involved in the production of cysteinyl leukotrienes which are involved in inflammation, and AM-679 has anti-inflammatory effects in animal studies. (wikipedia.org)
  • 5‐Lipoxygenase (5‐LOX) catalyses two steps in the biosynthesis of leukotrienes (LTs), lipid mediators of inflammation derived from arachidonic acid. (els.net)
  • 5‐LOX produces 5‐HPETE, leukotrienes and together with other dioxygenases lipoxins. (els.net)
  • AA could be metabolized by two major pathways: lipoxygenase (LOX) pathway producing hydroxy derivatives and leukotrienes and the cyclooxygenase (COX) pathway producing various prostaglandins. (hindawi.com)
  • LY293111 was also known to have inhibitory effects on 5-lipoxygenase, which is upstream of the production of leukotrienes. (hindawi.com)
  • Zileuton (A-64077) is an orally active inhibitor of 5-lipoxygenase , and thus inhibits leukotrienes (LTB4, LTC4, LTD4, and LTE4) formation, used to decrease the symptoms of asthma. (selleckchem.com)
  • Biosynthesis inhibitors for leukotrienes in bronchial asthma. (semanticscholar.org)
  • Antileukotrienes having clinical usefulness in asthma include zileuton, which inhibits 5-lipoxygenase, an enzyme critical in the biosynthesis of leukotrienes, and leukotriene receptor antagonists (cinalukast, montelukast, zarirlukast, and others). (thefreedictionary.com)
  • It is also reported that 5-lipoxygenase (5-LOX) and its products, cysteinyl leukotrienes (CysLTs, namely LTC 4 , LTD 4 and LTE 4 ), as well as cysteinyl leukotriene receptor 1 (CysLT 1 R) are closely associated with astrocyte proliferation and glial scar formation after brain injury. (biomedcentral.com)
  • In an embodiment, 5-LO-catalyzed eicosanoid metabolites that may be controlled or affected by administering analogs or derivatives of carotenoids to a subject may include proinflammatory effector molecules (e.g., leukotrienes). (google.es)
  • The inflammatory environment within the atherosclerotic lesion stimulates the 5-lipoxygenase pathway of arachidonic acid metabolism, leading to the biosynthesis of the potent lipid inflammatory mediators leukotrienes. (eurekaselect.com)
  • 1993) 5‐Lipoxygenase‐activating protein stimulates the utilization of arachidonic acid by 5‐lipoxygenase. (els.net)
  • The third pathway for metabolizing arachidonic acid, the lipoxygenase pathway catalyzes the incorporation of one oxygen molecule into polyunsaturated fatty acids to yield a 1-hydroperoxy-2, 4-trans, cis-pentadiene product [ 14 - 16 ]. (hindawi.com)
  • We selected most pathways alox5ap participated on our site, such as Arachidonic acid metabolism, Eicosanoid Synthesis, IL-5 Signaling Pathway, which may be useful for your reference. (creativebiomart.net)
  • BACKGROUND: Products of the arachidonic acid-metabolizing enzyme, 5-lipoxygenase, stimulate the growth of several cell types. (glycosciences.de)
  • Inhibitors of the Arachidonic Acid Pathway and Peroxisome Proliferator-activated Receptor Ligands Have Superadditive Effects on Lung Cancer Growth Inhibition Cancer Research. (jove.com)
  • Pubmed ID: 15899809 Arachidonic acid (AA) metabolizing enzymes and peroxisome proliferator-activated receptors (PPARs) have been shown to regulate the growth of epithelial cells. (jove.com)
  • 5. The method of claim 1 , wherein the formulation is adapted to deliver a dosage of synthetic carotenoid analog or a carotenoid derivative to the subject such that the levels of 5-HETE and the 5- HETE/arachidonic acid ratio in fluid samples collected from the subject are reduced. (google.es)
  • Precursor Arachidonic acid 5-hydroperoxide. (arragons-triathlon.club)
  • Inhibition of bile acid (BA) transport may contribute to the hepatotoxicity of troglitazone (TRO), a peroxisome proliferator-activated receptor gamma agonist. (biomedsearch.com)
  • Kehrer et al (2001) Inhibition of peroxisome-proliferator-activated receptor (PPAR)α by MK886. (tocris.com)
  • In summary, this investigation represents the first high-throughput screening designed to identify inhibitors of pol κ, with the characterization of biochemical and biologically relevant endpoints as a consequence of pol κ inhibition. (pubmedcentralcanada.ca)
  • In all cases, including the inhibition of MK886-induced 24p3 protein expression by stable transfection with antisense cDNA of 24p3, the extent of apoptosis closely paralleled 24p3 levels. (biochemj.org)
  • Here, we show that inhibition of 5-LO product formation by nonredox-type 5-LO inhibitors in human isolated polymorphonuclear leukocytes (PMNL) depends on the activation pathway of 5-LO. (nih.gov)
  • Thus, compared with 5-LO product synthesis induced by the Ca2+-mobilizing agent ionophore A23187, cell stress-induced 5-LO product formation involving 5-LO kinase pathways required ~10- to 100-fold higher concentrations of ZM230487 or L-739.010 for comparable 5-LO inhibition. (nih.gov)
  • Experiments using purified 5-LO revealed that Ca2+ is no prerequisite for potent enzyme inhibition by ZM230487, and exposure of PMNL to the combination of ionophore and cell stress did not restore potent 5-LO suppression. (nih.gov)
  • Antagonist activity of AM211 at the DP2 receptor was confirmed by inhibition of PGD 2 -stimulated guanosine 5′- O -[γ-thio]triphosphate binding to membranes expressing human DP2. (aspetjournals.org)
  • Study of the role of leukotriene B()4 in abnormal function of human subchondral osteoarthritis osteoblasts: effects of cyclooxygenase and/or 5-lipoxygenase inhibition. (semanticscholar.org)
  • Inhibition of 5-Lox induces apoptosis in prostate cancer cells by inactivating PKCε which is prevented by 5-oxoETE, and activators of PKCε prevent 5-Lox inhibition-induced apoptosis, suggesting that 5-Lox metabolites exert survival signaling via PKCε. (nih.gov)
  • Interestingly, we found that U73122, an inhibitor of PLC-beta, interrupts the apoptosis-preventing effect of 5-oxoETE, and exogenous diacyl-glycerol effectively prevents 5-Lox inhibition-induced apoptosis, suggesting that 5-oxoETE signals via OXER1 to promote prostate cancer cell survival. (nih.gov)
  • Effect of 5-Lox inhibition on prostate cancer cell survival. (nih.gov)
  • In the present paper, we studied the effect of pharmacologic inhibition of 5-lipoxygenase activating protein on the amyloidotic phenotype of Tg2576 mice. (biomedcentral.com)
  • These data establish a novel functional role for 5-lipoxygenase activating protein in the pathogenesis of Alzheimer's disease-like amyloidosis, and suggest that its pharmacological inhibition could provide a novel therapeutic opportunity for Alzheimer's disease. (biomedcentral.com)
  • It was further demonstrated that the they caused apoptosis based on the cell cycle arrest at SubG1/G1 phase, inhibition of Akt protein phosphorylation and also by causing increased amounts of cleaved PARP in tested cell lines. (wixsite.com)
  • ALOX5AP (Arachidonate 5-Lipoxygenase Activating Protein) is a Protein Coding gene. (genecards.org)
  • Associations of genetic polymorphisms of arachidonate 5-lipoxygenase-activating protein with risk of coronary artery disease in a European-American population. (cdc.gov)
  • α-Ketoglutarate (αKG) dependent oxygenases comprise a large superfamily of enzymes that activate O2 for varied reactions. (readbyqxmd.com)
  • We also studied expression of the enzymes that control their formation to understand how the 5-lipoxygenase (5-LO) pathway is activated in the coronary arteries. (ahajournals.org)
  • Protein Kinases are enzymes which catalyze the addition of a phosphate (PO43-) group to a substrate protein. (biovision.com)
  • Kermode J C et al: "Characteristics of binding of a potent chemotactic formyl tetrapeptide, formylmethionyl-leucyl-phenylalanyl-phenyl alanine, to the receptors on rabbit neutrophils" Journal of Leukocyte Biology vol. 43, No. 5, 1988, pp. 420-428, XP001029129 ISSN: 0741-5400. (freepatentsonline.com)
  • P2 purine and pyrimidine receptors: emerging superfamilies of G-protein-coupled and ligand-gated ion channel receptors", Eur. (patentgenius.com)
  • PGD 2 binds to three G protein-coupled receptors within the prostanoid family, namely PGD 2 receptor type 1 (DP1), PGD 2 receptor type 2 [DP2 or CRTH2, chemoattractant receptor-homologous molecule expressed on T helper 2 (Th2) cells], and the thromboxane A 2 receptor (TP). (aspetjournals.org)
  • Leukotriene Receptor (cys-LTs) are a family of potent bioactive lipids that act through two structurally divergent G protein-coupled receptors, termed the CysLT1 and CysLT2 receptors. (medchemexpress.com)
  • Leukotriene Receptor is a member of the superfamily of G protein-coupled receptors and uses a phosphatidylinositol-calcium second messenger system. (medchemexpress.com)
  • Although an inhibitor of leukotriene biosynthesis and antagonists of the cysteinyl leukotriene receptor are clinically used for bronchial asthma and allergic rhinitis, these medications were developed before the molecular identification of leukotriene receptors. (jci.org)
  • Currently, while only 5-lipoxygenase inhibitors and cysteinyl leukotriene receptor 1 (CysLT 1 ) antagonists are marketed to treat bronchial asthma and allergic rhinitis, other targets for at least four distinct types of receptors or their combinations are under consideration. (jci.org)
  • Two G protein-coupled receptors (GPCRs) have been cloned as receptors for leukotriene B 4 (LTB 4 ) ( Table 1 and refs. (jci.org)
  • In primary cultures of rat astrocytes, the effects of TGF-β1 and CysLT receptor agonists on migration and proliferation were assayed, and the expression of 5-LOX, CysLT receptors and TGF-β1 was detected. (biomedcentral.com)
  • The increased fluorescence seen in MK886-treated cells loaded with carboxydichlorofluorescein indicates that oxidative reactions are stimulated by this compound, possibly via the release of fatty acids from fatty acid-binding proteins and their subsequent oxidation. (portlandpress.com)
  • Following platelet-activating factor-induced shock, MK886 increased survival exclusively in female mice, and this effect was abolished by testosterone administration. (jci.org)
  • Exposure of murine prolymphoid progenitor cells (FL5.12) to 20 μM MK886 for 16 h dramatically increased 24p3 mRNA and protein expression. (biochemj.org)
  • The induction of 24p3 by MK886 was dependent on the synthesis of new protein(s), since cycloheximide, an inhibitor of protein synthesis, prevented this effect. (biochemj.org)
  • Selective inhibitors of the enzyme, including SC41661A and MK886, reduce PC-3 prostate cell proliferation. (glycosciences.de)
  • MK886, a 5-lipoxygenase-inhibitor with a different mechanism of action, induced nonnecrotic changes largely confined to the cytoplasm, most consistent with type 2 'autophagic' programmed cell death. (glycosciences.de)
  • This study compares the efficacy of intraplantar administration of indomethacin (a non-selective inhibitor of cyclooxygenase) and MK886 (an inhibitor of 5-lipoxygenase-activating protein), separately or in combination to produce preemptive analgesia in a model of surgical incisional pain in male Wistar rats. (bvsalud.org)
  • Exploring the function of PPAR , in this new context, may provide a better mechanistic model of its role in cancer and give an opportunity to design a more efficient therapeutic approach in combination with LOX/COX inhibitors. (hindawi.com)
  • It has also been reported that products of the LOX pathway and inhibitors of this pathway may induce activity of peroxisome-proliferator-activated receptor gamma (PPAR γ ) [ 9 , 16 , 17 ]. (hindawi.com)
  • Several synthetic ligands activate PPAR γ and reduce cell growth by inducing apoptosis in lung cancer [ 19 , 20 ]. (hindawi.com)
  • Combination therapy of 5-LOX inhibitor, PPAR γ ligand, and PPAR γ binding partner has resulted in an additive effect on cell growth decrease and induction of apoptosis [ 21 ]. (hindawi.com)
  • Separate lines of research have identified the 5-lipoxygenase/leukotriene B 4 receptor pathway and the PPAR pathway as potential targets for prevention or treatment of this disease. (hindawi.com)
  • Nordihydroguaiaretic acid (NDGA) is a cytotoxic insulin-like growth factor-I receptor (IGF-1R)/HER2 inhibitor and induces apoptosis . (selleckchem.com)
  • Receptor-interacting protein kinase 1 (RIPK1) induces apoptosis and necroptosis via kinase-dependent mechanisms and exhibits kinase-independent prosurvival and proinflammatory functions. (jci.org)
  • Protein Kinases thus form a very critical component of cellular signal transduction networks controlling nearly every aspect of cellular function from cell division to apoptosis. (biovision.com)
  • Inhibitors of its function impede translocation of 5-lipoxygenase from the cytoplasm to the cell membrane and inhibit 5-lipoxygenase activation. (genecards.org)
  • Omega 3 fatty acids inhibit tumor growth by a number of mechanisms including suppression of COX-2 expression and, for EPA at least, the alternative substrate produces different cyclooxygenase (PGE 3 ) and lipoxygenase (LTB 5 ) products that have anti-inflammatory and anticancer effects. (hindawi.com)
  • Malotilate is a liver protein metabolism improved compound, which selectively inhibit the 5-lipoxygenase . (selleckchem.com)
  • Compounds that bind to and inhibit the action of 5-LIPOXYGENASE-ACTIVATING PROTEINS. (bvsalud.org)
  • Unexpectedly, some CDK inhibitors (including flavopiridol, SNS-032 and roscovitine) are also proven to inhibit angiogenesis [56-60]. (angiogenesis-blog.com)
  • The drugs used to treat the patent ductus arteriosus are ibuprofen and indomethacin which are potent non-selective inhibitors of cyclo-oxygenase (COX) and therefore inhibit prostaglandin E2 synthesis. (bvsalud.org)
  • Also, other proteins which involved in the same pathway with alox5ap were listed below. (creativebiomart.net)
  • Some of the functions are cooperated with other proteins, some of the functions could acted by alox5ap itself. (creativebiomart.net)
  • We selected most functions alox5ap had, and list some proteins which have the same functions with alox5ap. (creativebiomart.net)
  • alox5ap has direct interactions with proteins and molecules. (creativebiomart.net)
  • We selected proteins and molecules interacted with alox5ap here. (creativebiomart.net)
  • Association between the polymorphism (rs17222919, -1316T/G) of 5-lipoxygenase-activating protein gene (ALOX5AP) and the risk of stroke: A meta analysis. (cdc.gov)
  • Role of adiponectin/peroxisome proliferator-activated receptor alpha signaling in human chorionic gonadotropin-induced estradiol synthesis in human luteinized granulosa cells. (abcam.com)
  • Dixon et al (1990) Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis. (tocris.com)
  • This gene encodes a protein which, with 5-lipoxygenase, is required for leukotriene synthesis. (genecards.org)
  • Inhibiting the 5-lipoxygenase pathway through either leukotriene synthesis inhibitors or leukotriene receptor antagonists in experimental models of atherosclerosis has however generated contradictory results. (eurekaselect.com)
  • Nordihydroguaiaretic acid (NDGA) inhibits p300 and activates autophagy . (selleckchem.com)
  • U73122 potently inhibits human 5-lipoxygenase (5-LO) . (selleckchem.com)
  • 4',5-Dihydroxyflavone inhibits soybean LOX-1 and yeast α-glucosidase . (selleckchem.com)
  • 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1 H -pyrrolizin-5-yl] acetic acid], currently undergoing phase III trials for osteoarthritis, inhibits the prostaglandin (PG) and leukotriene biosynthetic pathway. (aspetjournals.org)
  • Zileuton is a specific inhibitor of 5-lipoxygenase and thus inhibits leukotriene (LTB4, LTC4, LTD4, and LTE4) formation. (wikipedia.org)
  • Pectolinarigenin, an active anti-inflammatory ingredient in Cirsium chanroenicum , is a dual inhibitor of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) . (selleckchem.com)
  • Phenidone (1-phenyl-3-pyrazolidinone), a dual inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX) , is an organic compound that is primarily used as a photographic developer. (selleckchem.com)
  • OBJECTIVE: To find previously unknown properties of ML3000, a competitive inhibitor of the cyclooxygenase and the lipoxygenase (LO) pathway. (uzh.ch)
  • 19 In addition, inhibitors of 5-LO 20 and cysteinyl leukotriene receptor antagonists 21 are effective in reducing infarct size and reperfusion-induced arrhythmias in animal models of experimental ischemia. (ahajournals.org)
  • Discovery and mapping of ten novel G protein-coupled receptor genes", Gene, vol. 275, pp. 83-91 (2001). (patentgenius.com)
  • Quiflapon sodium (MK591) down regulates three genes [for cathepsin L, IL-17 and guanylate binding protein (GBP)-2] that are up regulated by SEB [1] . (medchemexpress.com)
  • Genes of the 5-lipoxygenase pathway are compelling candidates for atherosclerosis. (core.ac.uk)
  • The human genome contains ~ 500 protein kinase genes constituting a whopping 2% of the total number of human genes. (biovision.com)
  • Genetic variations within the genes encoding these proteins have been associated with cardiovascular risk. (eurekaselect.com)
  • Effects of 5-oxoETE on MK591-induced loss of PKCε activity in prostate cancer cells and on the activity of isolated PKCε in cell-free system. (nih.gov)
  • Then the cells were treated with MK591 (10 μM) with or without 5-oxoETE (10 μM) for 8 h. (nih.gov)
  • In (b), PKCε was first isolated from untreated LNCaP cells and then treated with 5-oxoETE or MK591 (10 μM) for 10 min in the assay buffer. (nih.gov)
  • Quiflapon sodium (MK591) influences cAMP response element-binding protein but not Sp1 [4] . (medchemexpress.com)
  • Effect of 5-lipoxygenase inhibitor MK591 on early molecular and signaling events induced by staphylococcal enterotoxin B in human peripheral blood mononuclear cells. (medchemexpress.com)
  • Ischemic stroke risk in a southeastern Chinese population: Insights from 5-lipoxygenase activating protein and phosphodiesterase 4D single-nucleotide polymorphisms. (cdc.gov)
  • TGF-β1-induced astrocyte migration was potentiated by LTD 4 , but attenuated by the 5-LOX inhibitor zileuton and the CysLT 1 R antagonist montelukast. (biomedcentral.com)
  • Examples of 5-LOX inhibitors include drugs, such as meclofenamate sodium [10] and zileuton . (wikipedia.org)
  • 5‐LOX products are involved in inflammation, allergic reactions, development of cardiovascular disease as well as certain types of cancer. (els.net)
  • LT biosynthesis inhibitors are currently under clinical investigation as treatments for respiratory and cardiovascular diseases. (jci.org)
  • However, specific COX-inhibitors have been correlated with an increased cardiovascular risk. (hindawi.com)
  • However, specific COX-2 inhibitors have been associated with cardiovascular toxicity [ 12 - 15 ]. (hindawi.com)
  • New COX/LOX inhibitors have been recently reported and initially these drugs showing a more favorable GI and cardiovascular tolerability [ 26 ]. (hindawi.com)
  • COX-2-selective inhibitors were designed to minimize gastrointestinal complications of traditional NSAIDs, but recent clinical studies indicated small but significantly increased risks for cardiovascular events ( McGettigan and Henry, 2006 ). (aspetjournals.org)
  • Several inhibitors of the 5-lipoxygenase pathway are now evaluated in clinical trials of patients with cardiovascular disease. (eurekaselect.com)
  • Required for leukotriene biosynthesis by ALOX5 (5-lipoxygenase). (genecards.org)
  • Abietic acid, an abietane diterpenoid, inhibited soybean 5-lipoxygenase with an IC50 of 29.5 ± 1.29 μM. (selleckchem.com)
  • ML355 is a potent and selective inhibitor of human 12-Lipoxygenase with an IC50 of 290 nM and shows excellent selectivity over related lipoxygenases and cyclooxygenases. (selleckchem.com)
  • In this study, we developed potent inhibitors of platelet aggregation based on the 1,5-diarylpyrazol-3-carboxamide scaffold with IC50 values in low nanomolar range (5.7-83 nM). (wixsite.com)
  • The anti-angiogenic activity of many CDK inhibitors with different buildings, including roscovitine, develops at least partly 760937-92-6 IC50 from disturbance with CDK5 [60,64]. (angiogenesis-blog.com)
  • The crystal structure of the minimized α/β-hydrolase fold protein encoded by the gene TTHA1544 from T. thermophilus HB8 has been determined at 2.0 Å resolution. (iucr.org)
  • Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and enzyme binding . (genecards.org)
  • These proteins were isolated based on the regulation of the IL-2 gene in T-lymphocytes. (stanford.edu)
  • These studies suggest that chimeric proteins may be used to harness the unique targeting feature of AAV for gene therapy applications. (labome.org)
  • This gene encodes a member of the lipoxygenase family of proteins. (genecards.org)
  • ALOX15 (Arachidonate 15-Lipoxygenase) is a Protein Coding gene. (genecards.org)
  • Pines J, Hunter T. Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2. (labome.org)
  • The prostaglandin D 2 (PGD 2 ) receptor type 2 (DP2) is a G protein-coupled receptor that has been shown to be involved in a variety of allergic diseases, including allergic rhinitis, asthma, and atopic dermatitis. (aspetjournals.org)
  • A number of biological agents have been developed to target cytokines thought to play an important role in asthma pathogenesis [ 20 , 21 ], including monoclonal antibody blockers of TNF-α, IL-5, IL-4 and IL-13. (beds.ac.uk)
  • The less active inhibitor, SC45662 neither reduced proliferation nor induced DNA laddering. (glycosciences.de)
  • Common Polymorphisms in the 5-Lipoxygenase Pathway and Risk of Incident Myocardial Infarction: A Danish Case-Cohort Study. (cdc.gov)
  • 5‐LOX is also involved in the biosynthesis of anti‐inflammatory/pro‐resolving lipoxins. (els.net)
  • We conclude that licofelone suppresses inflammatory PGE 2 formation preferentially by inhibiting mPGES-1 at concentrations that do not affect COX-2, implying an attractive and thus far unique molecular pharmacological dynamics as inhibitor of COX-1, the 5-lipoxygenase pathway, and of mPGES-1. (aspetjournals.org)
  • Endothelin-1-induced macrophage inflammatory protein-1beta expression in monocytic cells involves hypoxia-inducible factor-1alpha and AP-1 and is negatively regulated by microRNA-195 J Immunol. (usc.edu)
  • These include biological agents targeting pro-inflammatory cytokines such as interleukin-5 and interleukin-13, inhaled ultra long-acting β 2 -agonists and once daily inhaled corticosteroids. (beds.ac.uk)
  • TGF-β1-induced astrocyte migration is, at least in part, mediated by enhanced endogenous CysLTs through activating CysLT 1 R. These findings indicate that the interaction between the cytokine TGF-β1 and the pro-inflammatory mediators CysLTs in the regulation of astrocyte function is relevant to glial scar formation. (biomedcentral.com)
  • No significant differences were found between smokers and ex-smokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum. (biomedcentral.com)
  • Pro-inflammatory, or classically activated macrophages (M1) display pro-inflammatory and cytotoxic properties and can eradicate intracellular pathogens. (biomedcentral.com)
  • However, licofelone efficiently blocked the conversion of PGH 2 to PGE 2 mediated by mPGES-1 (IC 50 = 6 μM) derived from microsomes of interleukin-1β-treated A549 cells, being about equipotent to 3-[1-(4-chlorobenzyl)-3- t -butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid (MK-886), a well recognized mPGES-1 inhibitor. (aspetjournals.org)
  • 1981) Inflammation 5(1):13-17. (freepatentsonline.com)
  • Further, lipoxygenase pathway SNPs that were associated with measures of atherosclerosis were associated with markers of inflammation (CRP, ICAM-1) and calcification (MGP). (core.ac.uk)
  • Amyloid β peptide (Aβ) deposition in the brains of mice receiving MK-591, a selective and specific 5-lipoxygenase activating protein inhibitor, was significantly reduced when compared with controls. (biomedcentral.com)
  • Finally those many efforts that have been put into expression of eukaryotic membrane proteins are coming to fruition and enable to solve an ever-growing number of high resolution structures. (biomedcentral.com)
  • In the past, many skilful optimization steps were required to achieve sufficient expression of functional membrane proteins. (biomedcentral.com)
  • This review covers the most prominent solutions and pitfalls in expression of eukaryotic membrane proteins using microbial hosts (prokaryotes, yeasts), highlights skilful applications of our basic understanding to improve membrane protein production. (biomedcentral.com)
  • The discrepancy between biodiversity and poor structural knowledge can be largely attributed to the low natural expression of membrane proteins, to their hydrophobic character which complicates overexpression of functional membrane proteins, as well as to difficulties during their purification and crystallization. (biomedcentral.com)
  • Eukaryotic membrane proteins with high resolution structures. (biomedcentral.com)
  • 2. The method of claim 1 , wherein modulating the biological availability of eicosanoids in a subject comprises reducing the biological availability of eicosanoids formed by 5-lipoxygenase. (google.es)
  • a) Model of human wildtype 5‐LOX derived from the crystal structure of stable 5‐LOX (PDB: 3o8y). (els.net)
  • Allard JB and Brock TG (2005) Structural organization of the regulatory domain of human 5‐lipoxygenase. (els.net)
  • Selective upregulation of TNFα expression in classically-activated human monocyte-derived macrophages (M1) through pharmacological interference with V-ATPase. (nih.gov)
  • Monocyte Chemotactic and Activating Factor Is a Potent Histamine-releasing Factor for Human Basophils", The Journal of Experimental Medicine, vol. 175, Feb. 1992, pp. 489-493. (freepatentsonline.com)
  • Development, evaluation and application of 3D QSAR Pharmacophore model in the discovery of potential human renin inhibitors. (edu.au)
  • The feeding regimens were: human milk by breast feeding, a formula (F-I) containing 1.2 g/100 ml of protein and a control formula (F-II) containing 1.6 g protein/100 ml. (termsreign.gq)
  • Phosphorylation is the most widely prevalent bio-chemical modification (up to 30% of all human proteins can be regulated via phosphorylation) that can change the activity of a protein or regulate an enzyme by turning it on or off. (biovision.com)
  • 2,3-Dihydrobenzofuran privileged structures as new bioinspired lead compounds for the design of mPGES-1 inhibitors. (nih.gov)
  • B - Cell Activating Factor (BAFF) Inhibitors - Pipeline Insights, 2017" provides in depth insights on the pipeline drugs and their development activities around the B - Cell Activating Factor (BAFF) Inhibitors. (researchandmarkets.com)
  • Accessed 5 May 2017. (springer.com)
  • Lipoxygenases (LOXs) are a family of non-heme iron dioxygenases that are involved in the production and metabolism of fatty acid hydroperoxidases. (genecards.org)
  • Factor inhibiting HIF (FIH), initially isolated as a HIFα interacting protein following a yeast two-hybrid screen, is an asparaginyl hydroxylase that negatively regulates transcriptional activation by HIF. (readbyqxmd.com)
  • Activated Transcription Factor 3 in Association with Histone Deacetylase 6 Negatively Regulates MicroRNA 199a2 Transcription by Chromatin Remodeling and Reduces Endothelin-1 Expression Mol Cell Biol. (usc.edu)
  • Cellular 5‐LOX activity is regulated in a complex manner and depends on cellular localisation, phosphorylation, the intracellular calcium concentration and the redox status of the cell. (els.net)
  • 5‐LOX resides as soluble protein in the nucleoplasm or the cytsol, depending on the cell type and/or the phosphorylation status at Ser 271 or Ser 523 . (els.net)
  • Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. (nih.gov)
  • Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells. (nih.gov)
  • Kinases are turned on or off by phosphorylation (sometimes by the kinase itself - cis-phosphorylation also known as autophosphorylation), by binding of activator or inhibitor proteins, or small molecules, or by controlling their location in the cell relative to their substrates. (biovision.com)
  • Evaluation of Dual 5-Lipoxygenase/Microsomal Prostaglandin E2 Synthase-1 Inhibitory Effect of Natural and Synthetic Acronychia-Type Isoprenylated Acetophenones. (nih.gov)
  • Marmesin (S-(+)-Marmesin, (+)-Marmesin, (S)-Marmesin) is a natural coumarin with COX-2 and 5-LOX dual inhibitory activity. (selleckchem.com)
  • Magnus Back, " Inhibitors of the 5-Lipoxygenase Pathway in Atherosclerosis", Current Pharmaceutical Design (2009) 15: 3116. (eurekaselect.com)
  • The Case of Curcumin Prenylated Derivatives Acting as HDAC or mPGES-1 Inhibitors. (nih.gov)
  • The present invention provides small-molecule inhibitors of BMP signaling and compositions and methods for inhibiting BMP signaling. (organic-reaction.com)
  • Protein ligand interaction fingerprints are a powerful approach for the analysis and assessment of docking poses to improve docking performance in virtual screening. (readbyqxmd.com)
  • This allows the incorporation of known protein-ligand complex structures for a target-specific scoring. (readbyqxmd.com)
  • 12S-HHT is an endogenous ligand for BLT2 that fully activates BLT2 in vivo. (medchemexpress.com)
  • The total number of membrane protein structures deposited in the protein data bank (PDB) also strikingly reflects that membrane protein research can not yet keep pace with the one of soluble proteins. (biomedcentral.com)
  • 2008) The role of diacylglyceride generation by phospholipase D and phosphatidic acid phosphatase in the activation of 5‐lipoxygenase in polymorphonuclear leukocytes. (els.net)
  • U73122 is a potent phospholipase C (PLC) inhibitor, which reduces agonist-induced Ca 2+ increases in platelets and PMN. (selleckchem.com)
  • We found that prostate cancer cells express high levels of OXER1, a G protein-coupled 5-oxoETE receptor, which delivers signal by generating diacyl-glycerol through phospholipase C-beta. (nih.gov)
  • Our results show that expression of CLP was required for full cellular 5LO activity when cells were activated with Ca 2+ ionophore, as well as with a physiological stimulus (lipopolysaccharide followed by N-formylmethionyl-leucyl-phenylalanine). (pnas.org)
  • 5‐LOX is mainly expressed in myeloid and lymphoid cells and its expression is upregulated during cell differentiation. (els.net)
  • Compairing protein abundance and mRNA expression levels on a genomic scale, 2003, Genome Biology 4(9):117. (patentgenius.com)
  • 5-LO expression was determined by polymerase chain reaction and Western blot. (uzh.ch)
  • Peroxisome proliferator-activated receptor-a-mediated transcription of miR-199a2 attenuates endothelin-1 expression via hypoxia-inducible factor-1a J Biol Chem. (usc.edu)
  • Hypoxia-mediated expression of 5-lipoxygenase-activating protein involves HIF-1alpha and NF-kappaB and microRNAs 135a and 199a-5p J Immunol. (usc.edu)
  • Expression of 5-Lox was analyzed by Western blot (c). (nih.gov)
  • Optimization was performed individually for every membrane protein, but provided insight about commonly encountered bottlenecks and, more importantly, general guidelines how to alleviate cellular limitations during microbial membrane protein expression. (biomedcentral.com)
  • Lately, system-wide analyses are emerging as powerful means to decipher cellular bottlenecks during heterologous protein production and their use in microbial membrane protein expression has grown in popularity during the past months. (biomedcentral.com)
  • Actually, many years of strenuous efforts were required to get the proteins to crystals, relying on iterative optimization of all steps from expression to purification and crystallization. (biomedcentral.com)
  • On the other hand, TGF-β1 increased 5-LOX expression and the production of CysLTs, and up-regulated CysLT 1 R (not CysLT 2 R), while LTD 4 and N-methyl-LTC 4 did not affect TGF-β1 expression and release. (biomedcentral.com)
  • Downregulation of chemokine (C-X-C motif) ligands CXCL9, CXCL10 and CXCL11 was verified with Real-time polymerase chain reaction, CXCL10 protein levels were determined with ELISA. (uzh.ch)
  • However, mechanisms by which 5-Lox metabolites activate PKCε are not understood yet. (nih.gov)
  • In an embodiment, administering the analogs or derivatives of carotenoids embodied herein to a subject may control or affect the bioavailability of 5-LO-catalyzed eicosanoid metabolites. (google.es)