Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Genistein: An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.Benzamides: BENZOIC ACID amides.QuinazolinesReceptor, Epidermal Growth Factor: A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.PiperazinesReceptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Signal Transduction: 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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.src-Family Kinases: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.Tyrphostins: A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.Indoles: 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.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.Pyrroles: Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.Enzyme Activation: 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.Leukemia, Myelogenous, Chronic, BCR-ABL Positive: Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Cell Line, Tumor: A cell line derived from cultured tumor cells.Protein Tyrosine Phosphatases: An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.Lactams, Macrocyclic: LACTAMS forming compounds with a ring size of approximately 1-3 dozen atoms.Fusion Proteins, bcr-abl: Translation products of a fusion gene derived from CHROMOSOMAL TRANSLOCATION of C-ABL GENES to the genetic locus of the breakpoint cluster region gene on chromosome 22. Several different variants of the bcr-abl fusion proteins occur depending upon the precise location of the chromosomal breakpoint. These variants can be associated with distinct subtypes of leukemias such as PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; and NEUTROPHILIC LEUKEMIA, CHRONIC.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Benzoquinones: Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.Protein Kinase C: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Isoflavones: 3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position.Cells, Cultured: 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.Proto-Oncogene Proteins c-abl: Non-receptor tyrosine kinases encoded by the C-ABL GENES. They are distributed in both the cytoplasm and the nucleus. c-Abl plays a role in normal HEMATOPOIESIS especially of the myeloid lineage. Oncogenic transformation of c-abl arises when specific N-terminal amino acids are deleted, releasing the kinase from negative regulation.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.ThiazolesPyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.fms-Like Tyrosine Kinase 3: A receptor tyrosine kinase that is involved in HEMATOPOIESIS. It is closely related to FMS PROTO-ONCOGENE PROTEIN and is commonly mutated in acute MYELOID LEUKEMIA.Molecular Sequence Data: 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.Tumor Cells, Cultured: 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.Proto-Oncogene Proteins c-kit: A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.Mitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.Apoptosis: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Blotting, Western: 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.Phosphoproteinsp38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Proto-Oncogene Proteins pp60(c-src): Membrane-associated tyrosine-specific kinases encoded by the c-src genes. They have an important role in cellular growth control. Truncation of carboxy-terminal residues in pp60(c-src) leads to PP60(V-SRC) which has the ability to transform cells. This kinase pp60 c-src should not be confused with csk, also known as c-src kinase.Transfection: 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.Phenylurea Compounds: Compounds that include the amino-N-phenylamide structure.Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)Lung Neoplasms: Tumors or cancer of the LUNG.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Amino Acid Sequence: 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.Vanadates: Oxyvanadium ions in various states of oxidation. They act primarily as ion transport inhibitors due to their inhibition of Na(+)-, K(+)-, and Ca(+)-ATPase transport systems. They also have insulin-like action, positive inotropic action on cardiac ventricular muscle, and other metabolic effects.Lymphocyte Specific Protein Tyrosine Kinase p56(lck): This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.Intracellular Signaling Peptides and Proteins: 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.Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Protein Binding: 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.Tyrosine 3-Monooxygenase: An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 184.108.40.206.Epidermal Growth Factor: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.Proto-Oncogene Proteins c-fyn: Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Receptors, Vascular Endothelial Growth Factor: A family of closely related RECEPTOR PROTEIN-TYROSINE KINASES that bind vascular endothelial growth factors. They share a cluster of seven extracellular Ig-like domains which are important for ligand binding. They are highly expressed in vascular endothelial cells and are critical for the physiological and pathological growth, development and maintenance of blood and lymphatic vessels.Kinetics: The rate dynamics in chemical or physical systems.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.Focal Adhesion Kinase 2: A non-receptor protein-tyrosine kinase that is expressed primarily in the BRAIN; OSTEOBLASTS; and LYMPHOID CELLS. In the CENTRAL NERVOUS SYSTEM focal adhesion kinase 2 modulates ION CHANNEL function and MITOGEN-ACTIVATED PROTEIN KINASES activity.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.src Homology Domains: Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.Janus Kinase 2: A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.RNA, Messenger: 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.Proto-Oncogene Proteins c-met: Cell surface protein-tyrosine kinase receptors for HEPATOCYTE GROWTH FACTOR. They consist of an extracellular alpha chain which is disulfide-linked to the transmembrane beta chain. The cytoplasmic portion contains the catalytic domain and sites critical for the regulation of kinase activity. Mutations of the gene for PROTO-ONCOGENE PROTEINS C-MET are associated with papillary renal carcinoma and other neoplasia.Benzenesulfonates: Organic salts and esters of benzenesulfonic acid.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.Focal Adhesion Kinase 1: A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.Receptor, erbB-2: A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.Carcinoma, Non-Small-Cell Lung: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Receptors, Platelet-Derived Growth Factor: Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.Cyclin-Dependent Kinase Inhibitor p21: A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.MorpholinesProtein Structure, Tertiary: 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.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Calcium: 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.Recombinant Fusion Proteins: 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.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Phospholipase C gamma: A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesChromonesFlavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 220.127.116.11), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.Receptor, Platelet-Derived Growth Factor beta: A PDGF receptor that binds specifically to the PDGF-B chain. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.Xenograft Model Antitumor Assays: In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Cinnamatesp21-Activated Kinases: A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.Indole Alkaloids: Group of alkaloids containing a benzylpyrrole group (derived from TRYPTOPHAN)MAP Kinase Kinase 1: An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Gastrointestinal Stromal Tumors: All tumors in the GASTROINTESTINAL TRACT arising from mesenchymal cells (MESODERM) except those of smooth muscle cells (LEIOMYOMA) or Schwann cells (SCHWANNOMA).Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Carbazoles: Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.Down-Regulation: A negative 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.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.rho-Associated Kinases: A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.Angiogenesis Inhibitors: Agents and endogenous substances that antagonize or inhibit the development of new blood vessels.CDC2 Protein Kinase: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.Phthalazines1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine: A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.Catechols: A group of 1,2-benzenediols that contain the general formula R-C6H5O2.Ribosomal Protein S6 Kinases: A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.Pyrazoles: 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.Rats, Sprague-Dawley: 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.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Vascular Endothelial Growth Factor Receptor-2: A 200-230-kDa tyrosine kinase receptor for vascular endothelial growth factors found primarily in endothelial and hematopoietic cells and their precursors. VEGFR-2 is important for vascular and hematopoietic development, and mediates almost all endothelial cell responses to VEGF.Models, Biological: 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.Molecular Targeted Therapy: Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease.MAP Kinase Kinase Kinases: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).Proteins: 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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.RNA, Small Interfering: 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.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Receptor, Insulin: A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.Genes, abl: Retrovirus-associated DNA sequences (abl) originally isolated from the Abelson murine leukemia virus (Ab-MuLV). The proto-oncogene abl (c-abl) codes for a protein that is a member of the tyrosine kinase family. The human c-abl gene is located at 9q34.1 on the long arm of chromosome 9. It is activated by translocation to bcr on chromosome 22 in chronic myelogenous leukemia.Gene Expression Regulation: 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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.K562 Cells: An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Protein Tyrosine Phosphatase, Non-Receptor Type 11: A subtype of non-receptor protein tyrosine phosphatases that contain two SRC HOMOLOGY DOMAINS. Mutations in the gene for protein tyrosine phosphatase, non-receptor type 11 are associated with NOONAN SYNDROME.DNA-Binding Proteins: 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.Genes, erbB-1: The proto-oncogene c-erbB-1 codes for the epidermal growth factor receptor. Its name originates from the viral homolog v-erbB which was isolated from an avian erythroblastosis virus (AEV) where it was contained as a fragment of the chicken c-ErbB-1 gene lacking the amino-terminal ligand-binding domain. Overexpression of erbB-1 genes occurs in a wide range of tumors, commonly squamous carcinomas of various sites and less commonly adenocarcinomas. The human c-erbB-1 gene is located in the chromosomal region 7p14 and 7p12.Membrane Proteins: 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.Inhibitory Concentration 50: The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.HydroquinonesProtein Kinase C-delta: A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.QuinolinesCell Adhesion: Adherence of cells to surfaces or to other cells.Receptor, Platelet-Derived Growth Factor alpha: A PDGF receptor that binds specifically to both PDGF-A chains and PDGF-B chains. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.Oncogene Proteins v-abl: Transforming proteins encoded by the abl oncogenes. Oncogenic transformation of c-abl to v-abl occurs by insertional activation that results in deletions of specific N-terminal amino acids.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Aurora Kinases: A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.Receptor, IGF Type 1: A protein-tyrosine kinase receptor that is closely related in structure to the INSULIN RECEPTOR. Although commonly referred to as the IGF-I receptor, it binds both IGF-I and IGF-II with high affinity. It is comprised of a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The beta subunit contains an intrinsic tyrosine kinase domain.Reverse Transcriptase Polymerase Chain Reaction: 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.Drug Screening Assays, Antitumor: Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Creatine Kinase: A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.Up-Regulation: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Receptors, Growth Factor: Cell surface receptors that bind growth or trophic factors with high affinity, triggering intracellular responses which influence the growth, differentiation, or survival of cells.CDC2-CDC28 Kinases: A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.Casein Kinases: A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.MAP Kinase Kinase 4: A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.Proto-Oncogene Proteins c-yes: Members of the src-family tyrosine kinases that are activated during the transition from G2 PHASE to M PHASE of the CELL CYCLE. It is highly homologous to PROTO-ONCOGENE PROTEIN PP60(C-SRC).Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.MaleimidesBenzylidene Compounds: Compounds containing the PhCH= radical.eIF-2 Kinase: A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.Protein Processing, Post-Translational: 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.TOR Serine-Threonine Kinases: A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.Protein Kinase C-alpha: A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Receptor, trkA: A protein-tyrosine kinase receptor that is specific for NERVE GROWTH FACTOR; NEUROTROPHIN 3; neurotrophin 4, neurotrophin 5. It plays a crucial role in pain sensation and thermoregulation in humans. Gene mutations that cause loss of receptor function are associated with CONGENITAL INSENSITIVITY TO PAIN WITH ANHIDROSIS, while gene rearrangements that activate the protein-tyrosine kinase function are associated with tumorigenesis.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is PROTO-ONCOGENE PROTEINS C-MET.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.DNA Primers: 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.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Vascular Endothelial Growth Factor A: The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.Isoquinolines: A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Receptor, erbB-3: A cell surface protein-tyrosine kinase receptor that is specific for NEUREGULINS. It has extensive homology to and can heterodimerize with the EGF RECEPTOR and the ERBB-2 RECEPTOR. Overexpression of the erbB-3 receptor is associated with TUMORIGENESIS.1-Phosphatidylinositol 4-Kinase: An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.Carcinoma, Renal Cell: A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.
Tyrosine kinase inhibitors. Crystal structure of Abl kinase domain (blue) in complex with 2nd generation tyrosine kinase ... these regions are targeted in therapies to downregulate BCR-ABL kinase activity. Tyrosine kinase inhibitors specific to such ... a tyrosine kinase, and the BCR-Abl transcript is also translated into a tyrosine kinase containing domains from both the BCR ... Main article: Bcr-Abl tyrosine-kinase inhibitor. In the late 1990s, STI-571 (imatinib, Gleevec/Glivec) was identified by the ...
Tyrosine-kinase inhibitors ("-nib"). Receptor tyrosine kinase. *ErbB: HER1/EGFR (Brigatinib. *Erlotinib ... RET inhibitors: Vandetanib (also VEGFR and EGFR). Entrectinib (ALK, ROS1, NTRK). c-MET inhibitor: Cabozantinib (also VEGFR2). ...
... kinases. Afatinib is not only active against EGFR mutations targeted by first generation tyrosine-kinase inhibitors (TKIs) like ... Minkovsky N, Berezov A (December 2008). "BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors ... It belongs to the tyrosine kinase inhibitor family of medications. It is taken by mouth. ... RET inhibitors: Vandetanib (also VEGFR and EGFR). Entrectinib (ALK, ROS1, NTRK). c-MET inhibitor: Cabozantinib (also VEGFR2). ...
See also: Discovery and development of Bcr-Abl tyrosine kinase inhibitors. Nilotinib was developed by Novartis. It was ... 2010). "Extended kinase profile and properties of the protein kinase inhibitor nilotinib". Biochimica et Biophysica Acta (BBA ... Breccia, M.; Alimena, G. (2010). "Nilotinib: a second-generation tyrosine kinase inhibitor for chronic myeloid leukemia". ... "Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors". Drug Metabol Drug Interact. 29 (4): 249-59. doi:10.1515/ ...
Tyrosine-kinase inhibitors ("-nib"). Receptor tyrosine kinase. *ErbB: HER1/EGFR (Brigatinib. *Erlotinib ... Zhang J, Yang PL, Gray NS (Jan 2009). "Targeting cancer with small molecule kinase inhibitors". Nature Reviews. Cancer. 9 (1): ... RET inhibitors: Vandetanib (also VEGFR and EGFR). Entrectinib (ALK, ROS1, NTRK). c-MET inhibitor: Cabozantinib (also VEGFR2). ... especially those associated with receptor tyrosine kinases) is known as targeted therapy. ...
Inhibitors of Epidermal growth factor receptor (EGFR) *tyrosine kinase inhibitors (TKI's): *erlotinib (Tarceva)[ ... Ansari J, Palmer DH, Rea DW, Hussain SA (June 2009). "Role of tyrosine kinase inhibitors in lung cancer". Anti-Cancer Agents in ... Inhibitors of vascular endothelial growth factor (VEGF) *bevacizumab (Avastin)[unreliable medical source?] ... Inhibitor of EML4-ALK *crizotinib shows benefit in a subset of non-small cell lung cancer that is characterized by the EML4-ALK ...
... has recently been shown to be a potent inhibitor of JAK2V617F activity. JAK2V617F is a mutant of tyrosine kinase JAK2 ... As with other ATP competitive small molecule tyrosine kinase inhibitors, such as imatinib (Gleevec) in CML, patients rapidly ... It is a receptor tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR). ... "Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors". Drug Metabol Drug Interact. 29 (4): 1-11. doi:10.1515/dmdi- ...
Tyrosine kinase inhibitors (TKI) *Midostaurin. TKI acting on many different tyrosine kinases, approved by FDA and EMA for ... Proton pump inhibitors help reduce production of gastric acid, which is often increased in patients with mastocytosis. Excess ... Drugs to prevent/treat osteoporosis include Calcium-Vitamine D, bisphosphonates and in rare cases inhibitors of RANK-L ...
Tyrosine kinase inhibitors ("-nib"). Receptor tyrosine kinase. *ErbB: HER1/EGFR (Brigatinib. *Dacomitinib ... RET inhibitors: Vandetanib (also VEGFR and EGFR). Entrectinib (ALK, ROS1, NTRK). c-MET inhibitor: Cabozantinib (also VEGFR2). ... Ceritinib is an anaplastic lymphoma kinase (ALK)-positive inhibitor primarily used for the treatment of metastatic NSCLC. ... Ceritinib is a selective and potent inhibitor of anaplastic lymphoma kinase (ALK). In normal physiology, ALK functions as a key ...
... an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases". Cancer Research. 62 ( ... and RET tyrosine kinases. RET tyrosine kinases; it weakly inhibits VEGFR-3. ... "Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors". Drug Metabol Drug Interact. 0 (4): 249-59. doi:10.1515/dmdi ... "Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of tyrosine kinase inhibitors". Drug Metabol Drug Interact. 0 (3): 179- ...
2000). "Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino) ... It is an irreversible tyrosine-kinase inhibitor with activity against EGFR (IC50 0.8 nM), HER-2 (IC50 19 nM) and ErbB-4 (IC50 7 ... Khurana V, Minocha M, Pal D, Mitra AK (May 2014). "Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors". Drug ... "Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of tyrosine kinase inhibitors". Drug Metabol Drug Interact. 29 (3): 1- ...
Toceranib and masitinib, examples of receptor tyrosine kinase inhibitors, are used in the treatment of canine mast cell tumors ... September 2009). "Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT". PLoS ONE. 4 (9). doi: ... a Receptor Tyrosine Kinase Inhibitor, for the Treatment of Dogs with Recurrent (Either Local or Distant) Mast Cell Tumor ...
Bcr-Abl tyrosine-kinase inhibitor, especially the sections on Ponatinib development and binding "Iclusig (ponatinib) Tablets, ... It has a more aggressive course than CML and is often treated with a combination of chemotherapy and tyrosine kinase inhibitors ... It is a multi-targeted tyrosine-kinase inhibitor. Some forms of CML, those that have the T315I mutation, are resistant to ... but also its isoforms that carry mutations that confer resistance to treatment with existing tyrosine kinase inhibitors, ...
Many are tyrosine-kinase inhibitors. Imatinib mesylate (Gleevec, also known as STI-571) is approved for chronic myelogenous ... Janus kinase inhibitors, e.g. FDA approved tofacitinib ALK inhibitors, e.g. crizotinib Bcl-2 inhibitors (e.g. obatoclax in ... One of the most successful molecular targeted therapeutic is Gleevec, which is a kinase inhibitor with exceptional affinity for ... Gefitinib (Iressa, also known as ZD1839), targets the epidermal growth factor receptor (EGFR) tyrosine kinase and is approved ...
Experimental medications: sorafenib a combined Tyrosine protein kinases inhibitor. Scheduling of drug treatments and ... increased tyrosine phosphorylytion of the focal adhesion kinase, and activation and nuclear translocation of mitogen-activated ... and causes activation of the signaling tyrosine kinase receptors even under low circulating concentrations of growth factors. ... MMP-2 is unlike other MMP's as its activity is modulated by metalloproteases called tissue inhibitor of metalloproteases (TIMP ...
Before the advent of tyrosine kinase inhibitors, the median survival time for CML patients had been about 3-5 years from time ... 2003). "Tyrosine Kinase Inhibitors: Targeting Considerations". Holland-Frei Cancer Medicine (NCBI bookshelf book) (6th ed.). ... CML is largely treated with targeted drugs called tyrosine-kinase inhibitors (TKIs) which have led to dramatic improved long- ... Kimura S, Ashihara E, Maekawa T (Oct 2006). "New tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia". ...
2ivu: CRYSTAL STRUCTURE OF PHOSPHORYLATED RET TYROSINE KINASE DOMAIN COMPLEXED WITH THE INHIBITOR ZD6474 ... protein kinase activity. • kinase activity. • protein binding. • protein tyrosine kinase activity. • ATP binding. • Ras guanyl- ... transmembrane receptor protein tyrosine kinase activity. • receptor tyrosine kinase. • transmembrane signaling receptor ... 2ivv: CRYSTAL STRUCTURE OF PHOSPHORYLATED RET TYROSINE KINASE DOMAIN COMPLEXED WITH THE INHIBITOR PP1 ...
AZD4547 is a tyrosine kinase inhibitor which targets FGFR1-3. It has demonstrated early evidence of efficacy in gastric cancer ... which causes the tyrosine kinase domains to initiate a cascade of intracellular signals. On a molecular level these signals ... a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the ... Alofanib is a novel first-in-class allosteric small-molecular inhibitor of FGFR2. It binds to the extracellular domain of FGFR2 ...
... response to tyrosine kinase inhibitor in; 211980; EGFR Nonsmall cell lung cancer, somatic; 211980; IRF1 Nonsmall cell lung ... response to tyrosine kinase inhibitor in; 211980; EGFR Adenocarcinoma of lung, somatic; 211980; BRAF Adenocarcinoma of lung, ... GALNT3 Tyrosine kinase 2 deficiency; 611521; TYK2 Tyrosinemia type II; 277660; TAT Tyrosinemia type III; 276710; HPD Ullrich ... Lutheran inhibitor; 111150; KLF1 Bloom syndrome; 210900; RECQL3 Blue cone monochromacy; 303700; OPN1MW Blue-cone monochromacy; ...
"Fms/Trk tyrosine kinase inhibitor PLX7486". NCI Drug Dictionary. National Cancer Institute.. ... PLX7486 is a CSF1R antagonist and pan-TRK inhibitor in clinical trials for advanced solid tumors. ...
... is a small molecule HER2-selective tyrosine kinase inhibitor. It is an investigational drug for HER2-positive breast ...
Bcr-Abl tyrosine-kinase inhibitor History of cancer chemotherapy "Imatinib Mesylate". The American Society of Health-System ... The active sites of tyrosine kinases each have a binding site for ATP. The enzymatic activity catalyzed by a tyrosine kinase is ... Imatinib is a 2-phenyl amino pyrimidine derivative that functions as a specific inhibitor of a number of tyrosine kinase ... Druker BJ, Lydon NB (January 2000). "Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic ...
... (AV-951) is an oral VEGF receptor tyrosine kinase inhibitor. It completed a trial investigation for the treatment of ... A Study of Tivozanib (AV-951), an Oral VEGF Receptor Tyrosine Kinase Inhibitor, in the Treatment of Renal Cell Carcinoma, ...
... tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase inhibitors". Molecular Cancer Therapeutics. 5 (4): ... Linifanib (ABT-869) is a structurally novel, potent inhibitor of receptor tyrosine kinases (RTK), vascular endothelial growth ... It has much less activity (IC50s > 1 μM) against unrelated RTKs, soluble tyrosine kinases, or serine/threonine kinases. In vivo ... a multitargeted receptor tyrosine kinase inhibitor". Molecular Cancer Therapeutics. 5 (4): 995-1006. doi:10.1158/1535-7163.MCT- ...
The multitargeted tyrosine kinase inhibitor sorafenib (trade name Nexavar), which inhibits vascular endothelial growth factor ... BMS-540215, a dual tyrosine kinase inhibitor, shows potent and selective inhibition of VEGFR and fibroblast growth factor ... Brivanib alaninate is a multitargeted tyrosine kinase inhibitor (as is sorafenib). Brivanib alaninate also inhibits VEGFR and ... tyrosine kinases. BMS-540215 is an ATP-competitive inhibitor of human VEGFR-2, with an IC50 of 25 nmol/L and Ki of 26 nmol/L. ...
Bcr-Abl tyrosine-kinase inhibitors. *Cannabinoid receptor antagonists. *CCR5 receptor antagonists. *Neurokinin 1 receptor ...
Mental disorder or conscious disturbance in epidermal growth factor receptor-tyrosine kinase inhibitor treatment of advanced ... Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are currently recommended by international guidelines ... Epidermal growth factor receptor-tyrosine kinase inhibitor. Mental disorder. URI: http://hdl.handle.net/2003/39763. http://dx. ...
T1 - Erlotinib (OSI-774, Tarceva™), a selective epidermal growth factor receptor tyrosine kinase inhibitor, in combination with ... Erlotinib (OSI-774, Tarceva™), a selective epidermal growth factor receptor tyrosine kinase inhibitor, in combination with ... title = "Erlotinib (OSI-774, Tarceva™), a selective epidermal growth factor receptor tyrosine kinase inhibitor, in combination ... Erlotinib (OSI-774, Tarceva™), a selective epidermal growth factor receptor tyrosine kinase inhibitor, in combination with ...
... these mutations affect response to treatment with tyrosine kinase inhibitors. In the present study, we report on the molecular ...
A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Tyrosine kinases are enzymes ... Crystal structure of the second generation Bcr-Abl tyrosine-kinase inhibitor nilotinib (red) in complex with an Abl kinase ... Levitzki A, Mishani E (2006). "Tyrphostins and other tyrosine kinase inhibitors". Annu Rev Biochem. 75: 93-109. doi:10.1146/ ... "Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells". Nat Med. 2 (5): 561-6. ...
INHIBITORS PRESENTED BY: Y.VIJAY FINAL YEAR POST GRADUATEDEPARTMENT OF PHARMACOLOGY OSMANIA MEDICAL COLLEGE ... TYROSINE KINASE INHIBITORS * 1. TYROSINE KINASE INHIBITORS PRESENTED BY: Y.VIJAY FINAL YEAR POST GRADUATEDEPARTMENT OF ... 5. TYPES OF TYROSINE KINASES• Tyrosine kinases can be further subdivided into1. Receptor tyrosine kinases eg: EGFR, PDGFR, ... 9. TYROSINE KINASE INIBITORS1. BCR-ABL Tyrosine Kinase Inhibitors eg: Imatinib Mesylate, Dasatinib, and Nilotinib.2. Epidermal ...
... and methods of using them to treat tyrosine kinase-dependent diseases and conditions in mammals: wherein n is an integer, ... regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, ... a tyrosine kinase inhibitor, an inhibitor of epidermal-derived growth factor, an inhibitor of fibroblast-derived growth factor ... a tyrosine kinase inhibitor, an inhibitor of epidermal-derived growth factor, an inhibitor of fibroblast-derived growth factor ...
Smart drugs: tyrosine kinase inhibitors in cancer therapy.. Shawver LK1, Slamon D, Ullrich A. ... Protein-Tyrosine Kinases/antagonists & inhibitors*. *Protein-Tyrosine Kinases/metabolism. *Receptor Protein-Tyrosine Kinases/ ...
Drug-drug interactions with tyrosine-kinase inhibitors. [Lancet Oncol. 2014]. *Drug interactions between tyrosine-kinase ... Drug-drug interactions with tyrosine-kinase inhibitors: a clinical perspective.. van Leeuwen RW1, van Gelder T2, Mathijssen RH3 ... Drug interactions between tyrosine-kinase inhibitors and acid suppressive agents: more than meets the eye-Authors reply. [ ... We discuss all haemato-oncological and oncological tyrosine-kinase inhibitors that had been approved by Aug 1, 2013, by the US ...
... Opportunities and Market Forecast to 2026 - published on openPR ... Tyrosine Kinase Inhibitors. • Vascular Endothelial Growth Factor (VEGFR) Tyrosine Kinase Inhibitors. Global Tyrosine Kinase ... Tyrosine Kinase Inhibitors - Pipeline Insights 2017 The "Tyrosine kinase Inhibitors-Pipeline Insights 2017″ report provides a ... Tyrosine Kinase Inhibitors - Pipeline Insights 2017 The "Tyrosine kinase Inhibitors-Pipeline Insights 2017″ report provides a ...
The present invention provides methods for use of IL-21 in combination with a tyrosine kinase inhibitor (TKI) in treatment of ... Tyrosine kinases can be classified as receptor and nonreceptor protein tyrosine kinases. They play an essential role in diverse ... Some of the mutations identified are in B-Raf kinase, FLt3 kinase, BCR-ABL kinase, c-KIT kinase, epidermal growth factor (EGFR ... Tyrosine kinase inhibitors (TKIs) are small molecules that act inside the cell, competing with adenosine triphosphate (ATP) for ...
La Haute Autorité de santé, organisme public indépendant d'expertise scientifique, consultatif, formule des recommandations et rend des avis indépendants, impartiaux, faisant autorité, Low clinical benefit in the treatment of aggressive systemic mastocytosis (ASM), systemic mastocytosis associated with a second malignant blood disorder (SM-SBD) or mast cell leukaemia (MCL), but no demonstrated clinical advantage in the therapeutic strategy.
Tec kinases are the second largest group of nonreceptor tyrosine kinases and are closely related to the Src and Abl kinases (21 ... The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. Oliver Hantschel, Uwe Rix, Uwe Schmidt, Tilmann ... The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib ... The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib ...
Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice. Proc Natl Acad Sci U S A 2008;105:18895-18900 ... Improved Glycemic Control With the Multi-Receptor Tyrosine Kinase Inhibitor Pazopanib. Steffen Böhm, Dagmar Hess, Silke ... Improved Glycemic Control With the Multi-Receptor Tyrosine Kinase Inhibitor Pazopanib. Steffen Böhm, Dagmar Hess, Silke ... Improved Glycemic Control With the Multi-Receptor Tyrosine Kinase Inhibitor Pazopanib Message Subject (Your Name) has forwarded ...
Bcr-Abl tyrosine-kinase inhibitors (TKI) are the first-line therapy for most patients with chronic myelogenous leukemia (CML). ... An, X.; Tiwari, A.; Sun, Y.; Ding, P.; Ashby Jr, C.; Chen, Z. (2010). "BCR-ABL tyrosine kinase inhibitors in the treatment of ... Druker, B. J. and Lydon, N. B. (2000). "Lessons learned from the development of an Abl tyrosine kinase inhibitor for chronic ... Shawver, L. K., Slamon, D. and Ullrich, A. (2002). "Smart drugs:Tyrosine kinase inhibitors in cancer therapy". Cancer Cell: 117 ...
A Pharmacokinetic Study of Genistein, a Tyrosine Kinase Inhibitor. The safety and scientific validity of this study is the ... Genistein is a known protein-tyrosine kinase inhibitor, and in preclinical studies it has been shown to increase cell adhesion ... Genistein is a known protein-tyrosine kinase inhibitor, and in preclinical studies it has been shown to increase cell adhesion ... Protein Kinase Inhibitors. Enzyme Inhibitors. Molecular Mechanisms of Pharmacological Action. Phytoestrogens. Estrogens, Non- ...
Brutons tyrosine kinase in complex with a t-butyl cyanoacrylamide inhibitor. *DOI: 10.2210/pdb4YHF/pdb ... Prolonged and tunable residence time using reversible covalent kinase inhibitors.. Bradshaw, J.M., McFarland, J.M., Paavilainen ... Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Brutons tyrosine kinase (BTK) with ... The inverted cyanoacrylamide strategy was further used to discover fibroblast growth factor receptor (FGFR) kinase inhibitors ...
... inhibitors is described. Inhibition of spleen tyrosine kinase has attracted much attention as a mechanism for the treatment of ... A novel approach to design selective spleen tyrosine kinase (Syk) ... A novel approach to design selective spleen tyrosine kinase (Syk) inhibitors is described. Inhibition of spleen tyrosine kinase ... We report the structure-guided identification of three series of selective spleen tyrosine kinase inhibitors that support our ...
... cell growth is driven by a group of enzymes known as receptor tyrosine kinases. In the current issue of the Journal of Clinical ... New class of proteins allows breast cancer cells to evade tyrosine kinase inhibitors. JCI Journals ... New class of proteins allows breast cancer cells to evade tyrosine kinase inhibitors ... known as tyrosine kinase inhibitors (TKIs) have not been effective in treating breast cancer. Researchers believe that the ...
Importantly, we showed that tyrosine kinase inhibitor-resistant tumors, with EGFRT790M and EGFRC797S mutations, were highly ... BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations. PLoS Med. 2007;4( ... Notch inhibition overcomes resistance to tyrosine kinase inhibitors in EGFR-driven lung adenocarcinoma. Emilie Bousquet Mur,1 ... The RAS-related GTPase RHOB confers resistance to EGFR-tyrosine kinase inhibitors in non-small-cell lung cancer via an AKT- ...
Masitinib is a potent and selective tyrosine kinase inhibitor targeting KIT that is active, orally bioavailable in vivo, and ... Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT.. [Patrice Dubreuil, Sébastien Letard, Marco ... a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT. In vitro, masitinib had greater activity and ... selective nature of masitinib suggests that it will exhibit a better safety profile than other tyrosine kinase inhibitors; ...
The radiolabeled HER2-selective inhibitor 125/131I-IBA-CP is a promising probe for in vivo detection of HER2-positive tumors ... Conclusion: The radiolabeled HER2-selective inhibitor 125/131I-IBA-CP is a promising probe for in vivo detection of HER2- ...
Epidermal growth factor inhibitor Tyrosine kinase inhibitor Skin inflammation Antimicrobial peptide Cytokine Chemokine ... Hartmann JT, Haap M, Kopp HG, Lipp HP (2009) Tyrosine kinase inhibitors-a review on pharmacology, metabolism and side effects. ... Yamaki M, Sugiura K, Muro Y, Shimoyama Y, Tomita Y (2010) Epidermal growth factor receptor tyrosine kinase inhibitors induce ... Christensen JG (2007) A preclinical review of sunitinib, a multitargeted receptor tyrosine kinase inhibitor with anti- ...
Tyrosine kinase inhibitors target cancer stem cells in renal cell cancer.. [Anna M Czarnecka, Wojciech Solarek, Anna ... It was shown that the proliferation rate of cancer stem cells was decreased by the tyrosine kinase inhibitors. The efficacy of ... This study was designed to analyze the impact of multi-targeted tyrosine kinase inhibitors on the cancer stem cell ... Cells were treated with tyrosine kinase inhibitors, sunitinib, sorafenib and axitinib, in 2D and 3D culture conditions. Cell ...
Discrepancies between plasma, serum, whole blood and cellular concentrations of various tyrosine kinase inhibitors. R. ... targeted chemotherapeutic treatment consists of a series of small molecules collectively known as tyrosine kinase inhibitors ( ... Tyrosine kinase inhibitor pharmacokinetics. Tyrosine kinase inhibitor pharmacokinetics more * Department information * Staff ...
Lessons learned from the development of an Abl tyrosine kinase inhibitor for chronic myelogenous leukemia. ... Lessons learned from the development of an Abl tyrosine kinase inhibitor for chronic myelogenous leukemia. ... Model of STI 571 bound within the active site of the Abl kinase. (. a. ) Overlay of ATP (red) and STI 571 (orange). Key amino ...
TKIsTherapy with tyrosine kinase inhTumorsMutationsReceptor tyrosine kinaseImatinibPhosphorylationReceptorsInhibitsSunitinibSerineSignal transductionEpidermal growthClass of tyrosine kinase inhChronicVascular endothFibroblast growth fCompoundsGefitinibMulti-targeted tyrosineNilotinib2016Renal Cell CarcInhibit the tyrosine kinaseDasatinibPDGFRResistance to tyrosineProteinsResiduesToxicityPDGFSpleen tyrosinePotent and selectiveSeveral tyrosineSignaling pathwayTargetsProtein kinase inPathwaysPatientsFGFRLung adenocarcinomaCancersTumorProliferation
- Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. (nih.gov)
- The purpose of this study was to examine the relationship between mesangial cell proliferation and phosphorylated signal transducer and activator of transcription (STAT) 3 and to determine whether the PDGF receptor tyrosine kinase inhibitor STI 571 inhibited mesangial cell proliferation via modulation of STAT3. (ovid.com)
- We hypothesized that sunitinib malate, a receptor tyrosine kinase inhibitor, could reverse MDSC-mediated immune suppression and modulate the tumor microenvironment, thereby improving the efficacy of immune-based therapies. (aacrjournals.org)
- Sunitinib malate is an oral receptor tyrosine kinase inhibitor that inhibits some tumor growth. (aacrjournals.org)
- Kim WJ, Kim S, Choi H et al (2015) Histological transformation from non-small cell to small cell lung carcinoma after treatment with epidermal growth factor receptor-tyrosine kinase inhibitor. (springer.com)
- Pazopanib (GW786034) is a potent multi-targeted receptor tyrosine kinase inhibitor under clinical development for the treatment of age-related macular degeneration (via topical ophthalmic administration) and several cancers (via oral administration). (arvojournals.org)
- BCR-ABL Tyrosine Kinase Inhibitors eg: Imatinib Mesylate, Dasatinib, and Nilotinib.2. (slideshare.net)
- IMATINIB & NILOTINIB: bind to a segment of the kinase domain that fixes the enzyme in a closed or nonfunctional state, in which the protein is unable to bind its substrate/phosphate donor, ATP. (slideshare.net)
- Dasatinib is a small-molecule kinase inhibitor used for the treatment of imatinib-resistant chronic myelogenous leukemia (CML). (pnas.org)
- The small-molecule kinase inhibitor imatinib (Gleevec, Novartis) binds to the active site of the Bcr-Abl kinase domain and inhibits its constitutive tyrosine kinase activity ( 2 , 3 ). (pnas.org)
- Imatinib is a relatively weak inhibitor of Bcr-Abl, with an IC 50 in the upper nanomolar range, but has remarkable specificity, targeting only particular conformations of very few other kinases, mainly Abl family members, c-Kit and PDGF-R ( 5 - 8 ). (pnas.org)
- Therefore, kinase inhibitors targeting imatinib-resistant variants of Bcr-Abl have been developed. (pnas.org)
- Dasatinib inhibits Bcr-Abl kinase activity in the low-nanomolar range and inhibits all clinically relevant imatinib-resistant forms with the exception of the common T315I (gatekeeper) mutation ( 12 , 14 ). (pnas.org)
- In vitro, masitinib had greater activity and selectivity against KIT than imatinib, inhibiting recombinant human wild-type KIT with an half inhibitory concentration (IC(50)) of 200+/-40 nM and blocking stem cell factor-induced proliferation and KIT tyrosine phosphorylation with an IC(50) of 150+/-80 nM in Ba/F3 cells expressing human or mouse wild-type KIT. (sigmaaldrich.com)
- Due to increasing resistance and intolerance to imatinib efforts were made to develop new drugs that could inhibit the Bcr-Abl tyrosine kinase. (wikipedia.org)
- While drug screening was used to develop imatinib, second generation TKI's were developed with rational drug design approach due to increased knowledge in structural biology of the Bcr-Abl tyrosine kinase. (wikipedia.org)
- Imatinib (Gleevec) was discovered in 1992 and is regarded as first generation drug since it is the first Bcr-Abl tyrosine kinase inhibitor to be used in the treatment of CML. (wikipedia.org)
- In the development of imatinib, the structure of Bcr-Abl tyrosine kinase played a limited role because it was unknown. (wikipedia.org)
- Since then crystallographic studies have revealed that imatinib binds to the kinase domain of Abl only when the domain adopts the inactive or "closed" conformation. (wikipedia.org)
- In contrast to Imatinib, Dasatinib Src inhibitor also has verified to be more active . (selleckchem.com)
- As such, imatinib (Gleevec) is highly effective in chronic myeloid leukemia cells harboring the BCR-ABL translocation, gastrointestinal stromal tumor cells with activating mutations of C-KIT , and chronic myelomonocytic leukemia cells with rearrangements of the platelet-derived growth factor receptor, all of which are effectively targeted by the inhibitor ( 2 ⇓ - 4 ). (pnas.org)
- METHODS: Molecular dynamics (MD) simulations on the complex of imatinib with the wild-type, T315I mutant, and 10 other P-loop mutants of the tyrosine kinase BCR-ABL were performed to study the mechanism of imatinib resistance. (uptodate.com)
- The aim of this study was to investigate the role of platelet-derived growth factor (PDGF) and PDGF receptors (PDGFRs) in the proliferation of human glioblastoma cells as a prerequisite for a new therapeutic approach to the treatment of malignant brain tumors with selective tyrosine kinase inhibitors such as imatinib. (springer.com)
- This article reviews the links between the basic principles of the molecular biology of the signal transduction inhibitors and the molecular, pharmacological and clinical significance of the novel tyrosine kinase inhibitor, imatinib mesylate, which could prove to be extremely important in the treatment of chronic myelogenous leukemia . (termedia.pl)
- We decided to focus our attention on the tyrosine kinase oncogene bcr-abl and the novel signal transduction inhibitor Imatinib Mesylate, given their major clinical significance that we attempt to point out. (termedia.pl)
- This notion was seriously challenged by Mahon and colleagues, who introduced the concept of discontinuation of tyrosine kinase inhibitor treatment with the Stop Imatinib (STIM) trial. (ascopost.com)
- Imatinib is a tyrosine kinase receptor antagonist that inhibits the mutated tyrosine kinases such as Bcr-Abl, c-kit, and platelet-derived growth factor receptor (PDGFR) in some malignancies. (scielo.org.za)
- Despite a well-recognized clinical benefit of the 2nd-generation tyrosine kinase inhibitor nilotinib in patients with imatinib-resistant/-intolerant or newly diagnosed chronic myeloid leukemia, recent evidence suggests that nilotinib has a propensity to increase the risk of occlusive arterial events, especially in patients with pre-existing cardiovascular risk factors. (haematologica.org)
- They are also called tyrphostins , the short name for " tyrosine phosphorylation inhibitor ", originally coined in a 1988 publication, which was the first description of compounds inhibiting the catalytic activity of the epidermal growth factor receptor (EGFR). (wikipedia.org)
- The 1988 study was the first demonstration of a systematic search and discovery of small-molecular-weight inhibitors of tyrosine phosphorylation, which do not inhibit protein kinases that phosphorylate serine or threonine residues and can discriminate between the kinase domains of the EGFR and that of the insulin receptor . (wikipedia.org)
- Normally the level of cellular tyrosine kinase phosphorylation is tightly controlled by the antagonizing effect of tyrosine kinase and tyrosine phosphatases. (slideshare.net)
- In anassessment study related to Dasatinib's mode of action in CML cultures it was discovered that it is most effective CrKL phosphorylation inhibitor . (selleckchem.com)
- Five hundred eighteen such enzymes exist in the human genome, of which ∼90 selectively catalyze the phosphorylation of tyrosine hydroxyl groups ( 2 , 3 ). (aacrjournals.org)
- and also a decrease in insulin receptor substrate-1 Ser 307 phosphorylation in JNK and inhibitor of NF-κB kinase (IKKβ) activation in these tissues. (diabetesjournals.org)
- Insulin stimulates a signaling network composed of a number of molecules, initiating the activation of insulin receptor tyrosine kinase and phosphorylation of insulin receptor substrates, including insulin receptor substrate (IRS)-1 and IRS-2 ( 6 ⇓ - 8 ). (diabetesjournals.org)
- Following tyrosine phosphorylation, IRS-1/IRS-2 bind and activate the enzyme phosphatidylinositol 3-kinase (PI3-K). The activation of PI3-K increases serine phosphorylation of Akt, which is responsible for most of the metabolic actions of insulin, such as glucose transport, lipogenesis, and glycogen synthesis ( 7 , 8 ). (diabetesjournals.org)
- in particular, investigating the level of MKK7 phosphorylation in response to external stresses induced by the tyrosine kinase receptor inhibitor Sunitinib. (bmj.com)
- OVA-induced Src phosphorylation was abrogated by Src inhibitors, but not affected by inhibitors of EGFR and Rho-kinase. (ahajournals.org)
- Inhibitors of Src and EGFR, but not Rho-kinase, also blocked OVA-induced EGFR phosphorylation. (ahajournals.org)
- Furthermore, a metalloproteinase inhibitor TAPI-0 and an inhibitor of heparin-binding EGF not only abrogated the OVA-induced aortic contraction, but also OVA-induced EGFR and MYPT1 phosphorylation, suggesting the involvement of EGFR transactivation. (ahajournals.org)
- Dasatinib is an inhibitor of tyrosine kinases receptors so it acts as anti-RTKs. (selleckchem.com)
- The structural investigation revealed that Dasatinib IC50 for SRC tyrosine kinase receptors and ABL it is 0.55 and 3nm respectively . (selleckchem.com)
- However, current therapies targeting tyrosine kinase receptors have poor therapeutic outcomes. (dovepress.com)
- Cytosolic tyrosine kinases are intracellular, whereas receptor tyrosine kinases (RTK) possess both extracellular and intracellular domains and function as membrane spanning cell surface receptors. (aacrjournals.org)
- The fibroblast growth factors (FGFs) act via four receptor tyrosine kinases (FGF receptors (FGFRs)) to elicit diverse physiological responses. (nature.com)
- c-kit, a 145-kd transmembrane glycoprotein, is the normal cellular homologue of the viral oncogene v-kit and a member of the receptor tyrosine kinase subclass III family that includes receptors for platelet-derived growth factor (PDGF), macrophage colony-stimulating factor, and flt3 ligand. (bloodjournal.org)
- Of the identified pro-angiogenic factors, vascular endothelial growth factor (VEGF) is key, binding to two tyrosine kinase receptors, the VEGF receptor (VEGFR-1 and VEGFR-2) that also triggers MAPK signalling. (thyroidmanager.org)
- The tyrosine kinases are cell growth factor receptors and oncogene products, so they are the research targets for cell signaling, cell proliferation and carcinogenesis. (tcichemicals.com)
- A tyrosine kinase inhibitor ( TKI ) is a pharmaceutical drug that inhibits tyrosine kinases . (wikipedia.org)
- DDR1-IN-1 binds to DDR1 in the 'DFG-out' conformation and inhibits DDR1 autophosphorylation in cells at submicromolar concentrations with good selectivity as assessed against a panel of 451 kinases measured using the KinomeScan technology. (harvard.edu)
- Temsirolimus specifically inhibits the mammalian target of rapamycin (mTOR), a highly conserved serine/threonine kinase which regulates cell growth and metabolism in response to environmental factors. (clinicaltrials.gov)
- These findings show that STI 571 selectively inhibits c-kit tyrosine kinase activity and downstream activation of target proteins involved in cellular proliferation and survival. (bloodjournal.org)
- Dasatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), predominantly targets BCR-ABL and SRC oncoproteins and also inhibits off-target kinases, which may result in unexpected drug responses. (lu.se)
- ZD1839 (Iressa) is a small-molecular-weight, ATP-mimetic that specifically inhibits the EGFR tyrosine kinase. (nih.gov)
- Cells were treated with tyrosine kinase inhibitors, sunitinib, sorafenib and axitinib, in 2D and 3D culture conditions. (sigmaaldrich.com)
- Patients must have experienced disease progression or intolerable toxicity with a vascular endothelial growth factor (VEGF)-targeted tyrosine kinase inhibitor (TKI) (e.g. sorafenib, sunitinib, pazopanib). (clinicaltrials.gov)
- Conclusion The increase in p-MKK7 expression directly correlates with Sunitinib induced cardiotoxicity, suggesting that MKK7 could be an important intracellular signalling protein involved in tyrosine kinase inhibitor induced cardiotoxicity. (bmj.com)
- Axitinib, a next-generation tyrosine kinase inhibitor approved for second-line treatment of renal cell carcinoma, has been associated with much less toxicity than sunitinib and thus may be considered a better partner for combination therapy, Dr. Motzer said. (ascopost.com)
- Superior progression-free survival and response rates were achieved with the combination of the PD-L1 inhibitor avelumab and the next-generation tyrosine kinase inhibitor axitinib vs sunitinib, a current standard of care for the first-line treatment of advanced renal cell carcinoma. (ascopost.com)
- Kinases that phosphorylate serine and threonine residues, and3. (slideshare.net)
- 1 micromol/L) against unrelated RTKs, soluble tyrosine kinases, or serine/threonine kinases. (nih.gov)
- 1 μmol/L) against unrelated RTKs, soluble tyrosine kinases, or serine/threonine kinases. (aacrjournals.org)
- Serine/threonine kinases have been known as typical intracellular protein kinases. (tcichemicals.com)
- Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. (wikipedia.org)
- The present invention relates to compounds of the Formula I, the pharmaceutically acceptable salts and stereoisomers thereof, which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent. (google.com)
- Using biochemical and cell-based assays of receptor activation, signal transduction, proliferation, and apoptosis, we found that STI 571 inhibited the SLF-dependent activation of wild-type c-kit kinase activity. (bloodjournal.org)
- The present invention relates to novel compounds selected from 2-aminoaryloxazoles that selectively modulate, regulate, and/or inhibit signal transduction mediated by certain native and/or mutant tyrosine kinases implicated in a variety of human and animal diseases such as cell proliferative, metabolic, allergic and degenerative disorders. (google.com)
- Constantine Zografos G, John Domeyer P. Tyrosine kinase inhibitors and signal transduction: molecular biology and latest data. (termedia.pl)
- The importance of protein tyrosine kinases in signal transduction and the association of aberrant protein tyrosine kinase receptor and ligand expression with proliferative disorders make agents that modulate the activity of protein tyrosine kinases attractive therapeutic targets. (aspetjournals.org)
- Epidermal Growth Factor Receptor TyrosineKinase Inhibitors eg: Gefitinib, Lapatinib.3. (slideshare.net)
- Similarly, most non-small-cell lung cancers (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) appear to be highly sensitive to treatment with the specific EGFR inhibitors gefitinib (Iressa) and erlotinib (Tarceva) ( 5 ⇓ - 7 ). (pnas.org)
- Balagula Y, Garbe C, Myskowski PL, Hauschild A, Rapoport BL, Boers-Doets CB, Lacouture ME (2011) Clinical presentation and management of dermatological toxicities of epidermal growth factor receptor inhibitors. (springer.com)
- F. Meriggi and A. Zaniboni, "Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Elderly Patients with Advanced Non-Small Cell Lung Cancer," Current Gerontology and Geriatrics Research , vol. 2010, Article ID 348174, 8 pages, 2010. (hindawi.com)
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are used in the clinic to treat malignancies ( 1 ). (diabetesjournals.org)
- 2 ] Epidermal growth factor receptor status and anaplastic lymphoma kinase status are the two most investigated pathways regarding adenocarcinoma. (jcancer.org)
- We have examined the possible mechanisms of resistance to the epidermal growth factor receptor (EGFR) inhibitors in tumor cells with variable levels of EGFR. (nih.gov)
- Preclinical studies with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) suggested that these agents would be cytostatic ( 1 , 2 ). (aacrjournals.org)
- A convenient set consisting of five Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase (TK) inhibitors. (agscientific.com)
- In contrast, PD 166866 had no effect on c-Src, platelet-derived growth factor receptor-β, epidermal growth factor receptor or insulin receptor tyrosine kinases or on mitogen-activated protein kinase, protein kinase C and CDK 4 at concentrations as high as 50 μM. (aspetjournals.org)
- Jackman D, Pao W, Riely GJ et al (2010) Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. (springer.com)
- So far, no mechanism-based approaches are available to specifically counteract the adverse effects of anti-EGFR drugs or any other class of tyrosine kinase inhibitors. (springer.com)
- PD 166866, a member of a new structural class of tyrosine kinase inhibitors, the 6-aryl-pyrido[2,3- d ]pyrimidines, was identified by screening a compound library with assays that measure protein tyrosine kinase activity. (aspetjournals.org)
- Expression of Bcr-Abl, the oncogenic counterpart of the tyrosine kinase c-Abl, is the basis for chronic myelogenous leukemia (CML) ( 1 ). (pnas.org)
- Bcr-Abl tyrosine-kinase inhibitors (TKI) are the first-line therapy for most patients with chronic myelogenous leukemia (CML). (wikipedia.org)
- BCR-ABL1 mutations may cause resistance to tyrosine kinase inhibitor (TKI) therapy in patients with either chronic myelogenous leukemia (CML) or Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). (arupconsult.com)
- Background: Chronic myeloid leukemia (CML) treatment improved considerably after introduction of oral tyrosine kinase inhibitors (TKI). (jnccn.org)
- As tyrosine kinase inhibitors became the mainstay of therapy for patients with chronic myeloid leukemia (CML), our assumption has been that patients would have a favorable outcome as long as they continued receiving therapy. (ascopost.com)
- Treatment with tyrosine kinase inhibitor (TKI) significantly improves survival for patients with chronic myeloid leukemia (CML) , but it is financially costly and is associated with a significant reduction in health-related quality of life (HRQOL). (oncologynurseadvisor.com)
- Rigel Pharmaceuticals), an oral spleen tyrosine kinase (SYK) inhibitor, for the treatment of adults with chronic ITP who had an insufficient response to previous treatment. (ahdbonline.com)
- Fostamatinib disodium hexahydrate is the first SYK inhibitor approved by the FDA for the treatment of patients with chronic ITP. (ahdbonline.com)
- Vascular Endothelial Growth Factor TyrosineKinase Inhibitors eg. (slideshare.net)
- ABT-869 is a structurally novel, receptor tyrosine kinase (RTK) inhibitor that is a potent inhibitor of members of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor families (e.g. (nih.gov)
- Comparison of the antiangiogenic/vascular properties of the oral mammalian target of rapamycin (mTOR) inhibitor RAD001 (everolimus) and the vascular endothelial growth factor receptor (VEGFR) inhibitor vatalanib (PTK/ZK). (aacrjournals.org)
- Antiangiogenic and antivascular properties were studied using various models in vitro and in vivo and were compared with the pan-vascular endothelial growth factor receptor (VEGFR) inhibitor vatalanib (PTK/ZK), which showed similar but also dissimilar activity in the same models. (aacrjournals.org)
- The inverted cyanoacrylamide strategy was further used to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating the generalizability of the approach. (rcsb.org)
- Masitinib also potently inhibited recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. (sigmaaldrich.com)
- Compounds have been developed to selectively inhibit the tyrosine kinase. (wikipedia.org)
- Previous reports on other PDGFR kinase inhibitors noted that some of these compounds can inhibit the kinase activity of c-kit. (bloodjournal.org)
- Overall, this series of compounds could provide a promising starting point for further development of potent BTK inhibitors for B-cell malignancy treatment. (rsc.org)
- The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions mediated by Spleen Tyrosine Kinase (Syk). (patents.com)
- Here, we examined anticancer effects of ponatinib, a multi-targeted tyrosine kinase inhibitor, on glioblastoma cells both in the U87MG cell line and in the mouse xenograft model. (dovepress.com)
- This study was designed to analyze the impact of multi-targeted tyrosine kinase inhibitors on the cancer stem cell subpopulation in renal cell cancer. (sigmaaldrich.com)
- 1. A method of treating renal cell carcinoma or metastatic melanoma comprising co-administering to a patient a composition comprising IL-21 polypeptide and a composition comprising a tyrosine kinase inhibitor. (freepatentsonline.com)
- In the JAVELIN Renal 101 phase III study, the combination of the immune checkpoint inhibitor avelumab (Bavencio), a programmed death ligand-1 (PD-L1) blocking antibody, plus the tyrosine kinase inhibitor axitinib (Inlyta) significantly improved progression-free survival in previously untreated patients with advanced renal cell carcinoma, according to the results presented at the European Society for Medical Oncology (ESMO) 2018 Congress. (ascopost.com)
- JAVELIN Renal 101 is the first positive phase III study combining an immune checkpoint blocker with a tyrosine kinase inhibitor compared to a tyrosine kinase inhibitor alone in the first-line treatment of advanced renal cell carcinoma," commented lead author Robert Motzer, MD , of the Memorial Sloan Kettering Cancer Center, New York. (ascopost.com)
- DASATINIB: binds both the open and closed configuration of BCR-ABL kinase. (slideshare.net)
- We have analyzed the kinases targeted by dasatinib by using an unbiased chemical proteomics approach to detect binding proteins directly from lysates of CML cells. (pnas.org)
- Besides Abl and Src kinases, we have identified the Tec kinases Btk and Tec, but not Itk, as major binders of dasatinib. (pnas.org)
- The kinase activity of Btk and Tec, but not of Itk, was inhibited by nanomolar concentrations of dasatinib in vitro and in cultured cells. (pnas.org)
- Dasatinib has been developed as a Src/Abl inhibitor but subsequently has been shown to affect a wider array of kinases ( 11 ). (pnas.org)
- In addition, dasatinib has recently been used in a drug-target profiling approach by using a library of ≈150 selected recombinant kinases expressed as phage particle fusion proteins, of which 67 were bound by dasatinib ( 15 ). (pnas.org)
- We found that the Tec kinases Btk and Tec are among the most prominent targets of dasatinib in a variety of cell lines and primary cells. (pnas.org)
- The drug that is orally administered is Dasatinib SRC inhibitor . (selleckchem.com)
- The capability of Dasatinib to block several types of receptor tyrosine kinases has made it aencouraging choice to treat different types of cancer. (selleckchem.com)
- Dasatinib BCR-ABL inhibitor also has been seen to inhibit various sorts of RTKs at different intensities for example for Src family (c-Kit, eph kinases, Src) was seen to be inhibited at different specificities . (selleckchem.com)
- To study the effectiveness of Dasatinib in prostate cancer it has shown to block a number of signaling pathways such as SFKs, Src kinases, Lyn and p130CAS by stopping them . (selleckchem.com)
- By inhibiting immunoregulatory kinases, dasatinib may induce a reversible state of aberrant immune reactivity associated with good clinical responses and a distinct adverse effect profile. (lu.se)
- Dasatinib, another TKI, is a potent PDGFR inhibitor that causes fluid retention in up to 50% of patients. (scielo.org.za)
- Receptor tyrosine kinases eg: EGFR, PDGFR, FGFR2. (slideshare.net)
- STI 571 (formerly known as CGP 57148B) is a known inhibitor of the c-abl, bcr-abl, and platelet-derived growth-factor receptor (PDGFR) tyrosine kinases. (bloodjournal.org)
- STI 571 (formerly known as CGP 57148B), a 2-phenylaminopyrimidine derivative, is a known inhibitor of the c-abl, bcr-abl, and PDGF receptor (PDGFR) tyrosine kinases. (bloodjournal.org)
- 32 33 There is a close homology between the kinase domains of PDGFR and c-kit. (bloodjournal.org)
- With evidence supporting a critical role for PDGF in arterial repair and restenosis following angioplasty, we investigated the ability of a selective inhibitor of the PDGFr-tyrosine kinase (TK) to block restenosis following angioplasty. (ahajournals.org)
- New forms of resistance can arise as: missense mutations within the Abl kinase domain, over-expression of Bcr-Abl, increased production of transmembrane plasma proteins, or the constitutive activation of downstream signaling molecules such as Src-family kinases. (wikipedia.org)
- This reaction is catalyzed by protein kinases that transfer the γ-phosphate group of ATP to hydroxyl groups on target proteins ( 1 ). (aacrjournals.org)
- Translocations can also result in FGFR1 fusion proteins with constitutive kinase activity. (nature.com)
- The type I receptor tyrosine kinases constitute a family of transmembrane proteins involved in various aspects of cell growth and survival and have been implicated in the initiation and progression of several types of human malignancies. (aacrjournals.org)
- ErbB family proteins have functional tyrosine kinase catalytic domains, with the exception of ErbB-3, which acts as a noncatalytic partner to other ErbB family members. (aacrjournals.org)
- Protein tyrosine kinases are enzymes that phosphorylate proteins on specific tyrosine residues within the primary sequence of the proteins. (aspetjournals.org)
- Tyrosine kinase is an enzyme that phosphorylates the hydroxyl group of the side chain of tyrosine residues in proteins. (tcichemicals.com)
- When a protein kinase phosphorylates substrate proteins by transferring phosphate from ATP to a substrate protein, the three-dimensional structure of the substrate protein changes and its activity is altered. (tcichemicals.com)
- Critical oncogenic proteins, including receptor tyrosine kinases (RTKs) (e.g. (spandidos-publications.com)
- Furthermore, Hsp90 inhibitors are known to exert a radiosensitizing effect through hypoxia-inducible factor-1α (HIF-1α), ataxia-telangiectasia mutated (ATM), checkpoint kinase 1 (CHK1), WEE1 G 2 checkpoint kinase (WEE1) ( 18 - 21 ) and other radioresistance-related client proteins. (spandidos-publications.com)
- Protein kinases are a group of enzymes that possess a catalytic subunit that transfers the gamma (terminal)phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. (slideshare.net)
- Kinases with activity toward all three residues. (slideshare.net)
- Background -Platelet-derived growth factor (PDGF), a purported mediator of arterial response to injury, stimulates proliferation, chemotaxis, and matrix production by activation of its membrane receptor tyrosine kinase. (ahajournals.org)
- A cell-permeable piperazinyl-quinazoline carboxamide compound that acts as a potent, ATP-competitive, reversible, and selective inhibitor of PDGF receptor family of tyrosine kinases. (agscientific.com)
- Rational design of highly selective spleen tyrosine kinase inhibitors. (biomedsearch.com)
- We report the structure-guided identification of three series of selective spleen tyrosine kinase inhibitors that support our hypothesis, and offer useful guidance to other researchers in the field. (biomedsearch.com)
- Using an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrated biochemical residence times spanning from minutes to 7 d. (rcsb.org)
- Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. (sigmaaldrich.com)
- Here we report the discovery of a potent and selective DDR1 inhibitor, DDR1-IN-1, and present the 2.2 Å DDR1 co-crystal structure. (harvard.edu)
- These results highlight the discovery of PD 166866, a new nanomolar potent and selective small molecule inhibitor of the FGFR-1 tyrosine kinase with potential use as antiproliferative/antiangiogenic agent for such therapeutic targets as tumor growth and neovascularization of atherosclerotic plaques. (aspetjournals.org)
- Collectively, these observations have suggested that genetically defined subsets of cancers may share dependence on a specific signaling pathway and that small-molecule inhibitors targeting these pathways would be most effectively tested in patient populations identified by appropriate molecular markers. (pnas.org)
- A new business intelligence report released by Up Market Research with title "Global Tyrosine Kinase Inhibitors Market Research Report 2019" that targets and provides comprehensive market analysis with future prospects to 2026. (openpr.com)
- Because of these observations, we have been interested in the FGF receptor tyrosine kinases as targets for such proliferative diseases as cancer, atherosclerosis and restenosis. (aspetjournals.org)
- Any protein kinase inhibitor that interferes with the action of tyrosine kinase. (ebi.ac.uk)
- Bcr-Abl tyrosine-kinase inhibitor Protein kinase inhibitor Yaish P, Gazit A, Gilon C, Levitzki A (1988). (wikipedia.org)
- Aberrant regulation of cell growth pathways is required for normal cells to become cancerous, and in many types of cancer, cell growth is driven by a group of enzymes known as receptor tyrosine kinases (RTKs). (eurekalert.org)
- 12 Inappropriate activation of FGFRs and their downstream effector signalling pathways (for example, RAS-RAF-MEK1/2-ERK1/2, phosphoinositide-3 kinase, phospholipase-C gamma (PLCγ) and signal transducer and activator of transcription 3 (STAT3)) drives cell proliferation, survival and invasion. (nature.com)
- It has recently been observed that a modest number of patients, suffering from both malignancies and type 2 diabetes, were successfully treated not only for their malignancies but also for diabetes when given some tyrosine kinase inhibitors ( 2 ⇓ ⇓ - 5 ). (diabetesjournals.org)
- We could say that next to being able to give tyrosine kinase inhibitors to patients with CML to improve their life expectancy, the best thing we can do now is to take them away…sometimes. (ascopost.com)
- Acquired resistance to targeted tyrosine kinase inhibitors is a growing problem in the clinic but has not yet been explored for FGFR inhibitors. (nature.com)
- The success of FGFR inhibitors (FGFRi) will require knowledge of their cellular selectivity, determinants of intrinsic tumour cell sensitivity/resistance and the mechanisms by which tumour cells adapt (acquired resistance). (nature.com)
- Through direct synthetic efforts, we discovered a small molecule that is a nanomolar inhibitor of the human fibroblast growth factor-1 receptor (FGFR) tyrosine kinase. (aspetjournals.org)
- PD 166866 inhibited human full-length FGFR-1 tyrosine kinase with an IC 50 value of 52.4 ± 0.1 nM and was further characterized as an ATP competitive inhibitor of the FGFR-1. (aspetjournals.org)
- PD 166866 was a potent inhibitor of basic fibroblast growth factor (bFGF)-mediated receptor autophosphorylation in NIH 3T3 cells expressing endogenous FGFR-1 and in L6 cells overexpressing the human FGFR-1 tyrosine kinase, confirming a tyrosine kinase-mediated mechanism. (aspetjournals.org)
- This chapter is focused on potential application of noncoding RNAs in prediction of therapeutic response to tyrosine kinase inhibitors commonly used as targeted therapy in a wide range of metastatic cancers. (intechopen.com)
- Sequist LV, Waltman BA, Dias-Santagata D et al (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. (springer.com)
- Thus, in EGFR-expressing tumor cells with concomitant amplification(s) of PI3K-Akt signaling, combined blockade of the EGFR tyrosine kinase and Akt should be considered as a therapeutic approach. (nih.gov)
- 1 μmol/L), and in sensitive and insensitive tumor cells, pS6 kinase and 4E-BP1 were inhibited. (aacrjournals.org)
- However, ABT-869 exhibits potent antiproliferative and apoptotic effects on cancer cells whose proliferation is dependent on mutant kinases, such as FLT3. (nih.gov)
- The DDR1 receptor tyrosine kinase is activated by matrix collagens and has been implicated in numerous cellular functions such as proliferation, differentiation, adhesion, migration, and invasion. (harvard.edu)
- It was shown that the proliferation rate of cancer stem cells was decreased by the tyrosine kinase inhibitors. (sigmaaldrich.com)
- In contrast, the compound had no effect on MAP kinase activation or cellular proliferation in response to granulocyte-macrophage colony-stimulating factor. (bloodjournal.org)
- More importantly, inhibiting autophagy activities with pharmacologic inhibitors (BFA1, CQ or 3-MA) remarkably reduced the cell viabilities and clonal proliferation of T24 and J82 cells, compared to those treated with either of the agents alone. (mdpi.com)