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14-alpha Demethylase InhibitorsSterol 14-DemethylaseLanosterolHistone DemethylasesJumonji Domain-Containing Histone DemethylasesOxidoreductases, N-DemethylatingAllylamineCandida albicansSterolsAzolesEncyclopedias as TopicCytochrome P-450 Enzyme SystemCholestadienolsDrug Information ServicesNational Library of Medicine (U.S.)Counterfeit DrugsInternetGovernment AgenciesMEDLARSPortal VeinMagnaportheOryza sativaAspergillus oryzaePlant DiseasesFood SupplyFungal ProteinsArchivesAscomycotaBiological Science DisciplinesPeriodicals as TopicPubMedTriticumOrganophosphatesFluconazoleProdrugsInjections, IntravenousArea Under CurveDatabases, FactualAntifungal AgentsDrug Resistance, FungalMicrobial Sensitivity TestsChoice BehaviorDrug RepositioningDrug Resistance, MicrobialFungicides, IndustrialThiophanateCamphor 5-MonooxygenaseCrystallography, X-RayModels, MolecularTrypanosoma brucei bruceiProtein ConformationSleep
14-alpha Demethylase Inhibitors: Compounds that specifically inhibit STEROL 14-DEMETHYLASE. A variety of azole-derived ANTIFUNGAL AGENTS act through this mechanism.Sterol 14-Demethylase: An NADPH-dependent P450 enzyme that plays an essential role in the sterol biosynthetic pathway by catalyzing the demethylation of 14-methyl sterols such as lanosterol. The enzyme acts via the repeated hydroxylation of the 14-methyl group, resulting in its stepwise conversion into an alcohol, an aldehyde and then a carboxylate, which is removed as formic acid. Sterol 14-demethylase is an unusual cytochrome P450 enzyme in that it is found in a broad variety of organisms including ANIMALS; PLANTS; FUNGI; and protozoa.Lanosterol: A triterpene that derives from the chair-boat-chair-boat folding of 2,3-oxidosqualene. It is metabolized to CHOLESTEROL and CUCURBITACINS.Histone Demethylases: Enzymes that catalyse the removal of methyl groups from LYSINE or ARGININE residues found on HISTONES. Many histone demethylases generally function through an oxidoreductive mechanism.Jumonji Domain-Containing Histone Demethylases: A family of histone demethylases that share a conserved Jumonji C domain. The enzymes function via an iron-dependent dioxygenase mechanism that couples the conversion of 2-oxoglutarate to succinate to the hydroxylation of N-methyl groups.Oxidoreductases, N-DemethylatingAllylamine: Possesses an unusual and selective cytotoxicity for VASCULAR SMOOTH MUSCLE cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation.Candida albicans: A unicellular budding fungus which is the principal pathogenic species causing CANDIDIASIS (moniliasis).Sterols: Steroids with a hydroxyl group at C-3 and most of the skeleton of cholestane. Additional carbon atoms may be present in the side chain. (IUPAC Steroid Nomenclature, 1987)Azoles: Five membered rings containing a NITROGEN atom.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Cholestadienols: Cholestadiene derivatives containing a hydroxy group anywhere in the molecule.Drug Information Services: Services providing pharmaceutic and therapeutic drug information and consultation.National Library of Medicine (U.S.): An agency of the NATIONAL INSTITUTES OF HEALTH concerned with overall planning, promoting, and administering programs pertaining to advancement of medical and related sciences. Major activities of this institute include the collection, dissemination, and exchange of information important to the progress of medicine and health, research in medical informatics and support for medical library development.Counterfeit Drugs: Drugs manufactured and sold with the intent to misrepresent its origin, authenticity, chemical composition, and or efficacy. Counterfeit drugs may contain inappropriate quantities of ingredients not listed on the label or package. In order to further deceive the consumer, the packaging, container, or labeling, may be inaccurate, incorrect, or fake.Internet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.Government Agencies: Administrative units of government responsible for policy making and management of governmental activities.MEDLARS: A computerized biomedical bibliographic storage and retrieval system operated by the NATIONAL LIBRARY OF MEDICINE. MEDLARS stands for Medical Literature Analysis and Retrieval System, which was first introduced in 1964 and evolved into an online system in 1971 called MEDLINE (MEDLARS Online). As other online databases were developed, MEDLARS became the name of the entire NLM information system while MEDLINE became the name of the premier database. MEDLARS was used to produce the former printed Cumulated Index Medicus, and the printed monthly Index Medicus, until that publication ceased in December 2004.Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein.Magnaporthe: A genus of FUNGI, in the family Magnaporthaceae of uncertain position (incertae sedis). It is best known for its species, M. grisea, which is one of the most popular experimental organisms of all fungal plant pathogens. Its anamorph is PYRICULARIA GRISEA.Oryza sativa: Annual cereal grass of the family POACEAE and its edible starchy grain, rice, which is the staple food of roughly one-half of the world's population.Aspergillus oryzae: An imperfect fungus present on most agricultural seeds and often responsible for the spoilage of seeds in bulk storage. It is also used in the production of fermented food or drink, especially in Japan.Plant Diseases: Diseases of plants.Food Supply: The production and movement of food items from point of origin to use or consumption.Fungal Proteins: Proteins found in any species of fungus.ArchivesAscomycota: A phylum of fungi which have cross-walls or septa in the mycelium. The perfect state is characterized by the formation of a saclike cell (ascus) containing ascospores. Most pathogenic fungi with a known perfect state belong to this phylum.Biological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Triticum: A plant genus of the family POACEAE that is the source of EDIBLE GRAIN. A hybrid with rye (SECALE CEREALE) is called TRITICALE. The seed is ground into FLOUR and used to make BREAD, and is the source of WHEAT GERM AGGLUTININS.Organophosphates: Carbon-containing phosphoric acid derivatives. Included under this heading are compounds that have CARBON atoms bound to one or more OXYGEN atoms of the P(=O)(O)3 structure. Note that several specific classes of endogenous phosphorus-containing compounds such as NUCLEOTIDES; PHOSPHOLIPIDS; and PHOSPHOPROTEINS are listed elsewhere.Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal CANDIDIASIS and cryptococcal MENINGITIS in AIDS.Prodrugs: A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.Injections, Intravenous: Injections made into a vein for therapeutic or experimental purposes.Area Under Curve: A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)Databases, Factual: Extensive collections, reputedly complete, of facts and data garnered from material of a specialized subject area and made available for analysis and application. The collection can be automated by various contemporary methods for retrieval. The concept should be differentiated from DATABASES, BIBLIOGRAPHIC which is restricted to collections of bibliographic references.Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.Drug Resistance, Fungal: The ability of fungi to resist or to become tolerant to chemotherapeutic agents, antifungal agents, or antibiotics. This resistance may be acquired through gene mutation.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Choice Behavior: The act of making a selection among two or more alternatives, usually after a period of deliberation.Drug Repositioning: The deliberate and methodical practice of finding new applications for existing drugs.Drug Resistance, Microbial: The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Fungicides, Industrial: Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc.Thiophanate: Nematocide used in livestock; also has fungicidal properties.Camphor 5-Monooxygenase: A soluble cytochrome P-450 enzyme that catalyzes camphor monooxygenation in the presence of putidaredoxin, putidaredoxin reductase, and molecular oxygen. This enzyme, encoded by the CAMC gene also known as CYP101, has been crystallized from bacteria and the structure is well defined. Under anaerobic conditions, this enzyme reduces the polyhalogenated compounds bound at the camphor-binding site.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Trypanosoma brucei brucei: A hemoflagellate subspecies of parasitic protozoa that causes nagana in domestic and game animals in Africa. It apparently does not infect humans. It is transmitted by bites of tsetse flies (Glossina).Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Sleep: A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.

Tumor necrosis factor alpha increases P-glycoprotein expression in a BME-UV in vitro model of mammary epithelial cells. (1/31)

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Comparison of the inhibitory profiles of itraconazole and cimetidine in cytochrome P450 3A4 genetic variants. (2/31)

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Brain P450 epoxygenase activity is required for the antinociceptive effects of improgan, a nonopioid analgesic. (3/31)

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In vivo investigation in pigs of intestinal absorption, hepatobiliary disposition, and metabolism of the 5alpha-reductase inhibitor finasteride and the effects of coadministered ketoconazole. (4/31)

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Effects of strong CYP2D6 and 3A4 inhibitors, paroxetine and ketoconazole, on the pharmacokinetics and cardiovascular safety of tamsulosin. (5/31)

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Overexpression of CYP3A4, but not of CYP2D6, promotes hypoxic response and cell growth of Hep3B cells. (6/31)

Cytochrome P450s (P450s) contribute to carcinogenesis by activating procarcinogens and also metabolize anti-cancer drugs. The activity and protein levels of P450s are important in cancer risk and in cancer therapy. In this study, we found that overexpression of CYP3A4 induced growth of a human hepatoma cell line, Hep3B. Overexpression of CYP2D6, by comparison, decreased cell growth. An inhibitor of CYP3A4, ketoconazole, significantly suppressed the growth of Hep3B cells overexpressing CYP3A4, but an inhibitor of CYP2D6, quinidine, did not restore Hep3B cell growth to baseline levels. Overexpression of CYP3A4 increased the production of reactive oxygen species, but this was not the cause of the CYP3A4-induced growth. Previously, we showed that CYP3A4 can produce epoxyeicosatrienoic acids (EETs) from arachidonic acid. The CYP3A4-enhanced cell growth was attenuated by a putative EET receptor antagonist, 14,15-EEZE. CYP3A4 promoted progression of the cell cycle from the G1 to the S phase. CYP3A4 also induced a hypoxic response of Hep3B cells, detected as enhanced erythropoietin gene expression (a typical hypoxic response). The cell growth promoted by CYP3A4 was inhibited by PI3K inhibitor LY294002. These results suggest that CYP3A4 plays an important role in tumor progression, independent of the activation of carcinogens and metabolism of anti-cancer drugs.  (+info)

Substrate preferences and catalytic parameters determined by structural characteristics of sterol 14alpha-demethylase (CYP51) from Leishmania infantum. (7/31)

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Effectiveness of chronic treatment with ketoconazole in a patient with diabetic Cushing's disease resistant to surgery. (8/31)

Without treatment, Cushing's disease has significant morbidity and mortality. Where a surgical approach may not be feasible, or is refused by the patient, medical therapy becomes the only option. In this case report, we discuss the effects of two years of ketoconazole treatment on diabetes regulation and insulin resistance in a patient reluctant to agree to surgery. A 62 year-old female patient with uncontrolled type 2 diabetes mellitus was investigated. Cushing's disease was confirmed by the results of high urine free cortisol level and dexamethasone suppression tests. We discuss the effects of two years of 600 mg/day ketoconazole treatment on diabetes regulation and insulin resistance in a patient with Cushing's disease reluctant to agree to surgery. This case report illustrates the beneficial long-term effects of 24 months of ketoconazole treatment on the clinical and laboratory findings and also on steroid and glucose metabolism.  (+info)

Docking and Linking of Fragments To Discover Jumonji Histone Demethylase Inhibitors. - Nuffield Department of Orthopaedics,...Docking and Linking of Fragments To Discover Jumonji Histone Demethylase Inhibitors. - Nuffield Department of Orthopaedics,...
Development of tool molecules that inhibit Jumonji demethylases allows for the investigation of cancer-associated transcription. While scaffolds such as 2,4-pyridinedicarboxylic acid (2,4-PDCA) are potent inhibitors, they exhibit limited selectivity. To discover new inhibitors for the KDM4 demethylases, enzymes overexpressed in several cancers, we docked a library of 600,000 fragments into the high-resolution structure of KDM4A. Among the most interesting chemotypes were the 5-aminosalicylates, which docked in two distinct but overlapping orientations. Docking poses informed the design of covalently linked fragment compounds, which were further derivatized. This combined approach improved affinity by ∼ 3 log-orders to yield compound 35 (Ki = 43 nM). Several hybrid inhibitors were selective for KDM4C over the related enzymes FIH, KDM2A, and KDM6B while lacking selectivity against the KDM3 and KDM5 subfamilies. Cocrystal structures corroborated the docking predictions. This study extends the use of
Assessing histone demethylase inhibitors in cells: lessons learned. - PubMed - NCBIAssessing histone demethylase inhibitors in cells: lessons learned. - PubMed - NCBI
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
SELECTBIO - Epigenetics in Drug Discovery AgendaSELECTBIO - Epigenetics in Drug Discovery Agenda
This talk will describe our structure-based design approach towards the identification of potent JmjC histone demethylase inhibitors based upon the pyrido[3,4-d]pyrimidin-4(3H)-one scaffold which demonstrate potent and selective biochemical affinity for the KDM4 and KDM5 subfamily demethylases over the KDM2, KDM3 and KDM6 subfamilies and describe their cell-based activity profiles. ...
Applications filed at Nov 02 2017 | PURINONE DERIVATIVE HYDROCHLORIDE | Patents.comApplications filed at Nov 02 2017 | PURINONE DERIVATIVE HYDROCHLORIDE | Patents.com
PURINONE DERIVATIVE | PROCESS FOR MAKING TRICYCLIC LACTAM COMPOUNDS | Cis-tetrahydro-spiro(cyclohexane-1,1?-pyrido[3,4-b]indole)-4-amine Compounds | HISTONE DEMETHYLASE INHIBITORS | Fused Heterocyclic Compounds as Selective BMP Inhibitors |
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Quantitative High-Throughput Screening Identifies 8-Hydroxyquinolines as Cell-Active Histone Demethylase InhibitorsQuantitative High-Throughput Screening Identifies 8-Hydroxyquinolines as Cell-Active Histone Demethylase Inhibitors
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
SUBSTITUTED (E)-N-(1-PHENYLETHYLIDENE)BENZOHYDRAZIDE ANALOGS AS HISTONE DEMETHYLASE INHIBITORS - Patent applicationSUBSTITUTED (E)-N'-(1-PHENYLETHYLIDENE)BENZOHYDRAZIDE ANALOGS AS HISTONE DEMETHYLASE INHIBITORS - Patent application
0082] Suitable monovalent substituents on a substitutable carbon atom of an "optionally substituted" group are independently halogen; --(CH2)0-4R.sup.◯; --(CH2)0-4OR.sup.◯; --O(CH2)0-4R.sup.◯, --O--(CH2)0-4C(O)OR.sup.◯; --(CH2)0-4--CH(OR.sup.◯)2; --(CH2)0-4SR.sup.◯; --(CH2)0-4Ph, which may be substituted with R.sup.◯; --(CH2)0-4O(CH2)0-1Ph which may be substituted with R.sup.◯; --CH═CHPh, which may be substituted with R.sup.◯; --(CH2)0-4O(CH2)0-1-pyridyl which may be substituted with R.sup.◯; --NO2; --CN; --N3; --(CH2)0-4N(R.sup.◯)2; --(CH2)0-4N(R.sup.◯)C(O)R.sup.◯; --N(R.sup.◯)C(S)R.sup.◯; --(CH2)0-4N(R.sup.◯)C(O)NR.sup.◯2; --N(R.sup.◯)C(S)NR.sup.◯2; --(CH2)0-4N(R.sup.◯)C(O)OR.sup.◯; --N(R.sup.◯)N(R.sup.◯)C(O)R.sup.◯; --N(R.sup.◯)N(R.sup.◯)C(O)NR.sup.◯.su- b.2; --N(R.sup.◯)N(R.sup.◯)C(O)OR.sup..largecircle- .; --(CH2)0-4C(O)R.sup.◯; --C(S)R.sup.◯; --(CH2)0-4C(O)OR.sup.◯; --(CH2)0-4C(O)SR.sup.◯; --(CH2)0-4C(O)OSiR.sup.◯3; ...
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In this issue of Clinical Cancer Research, Huang and colleagues, characterize the effects of novel histone demethylase inhibitors, either alone or in combination with inhibitors of DNA methyltransferases (DNMTI), on the proliferation and survival of transformed cells (1). A widely accepted view holds that the origins of cancer lie, at least in part, in the silencing of genes responsible for cell death and/or differentiation, a phenomenon that generally stems from perturbations in the transcriptional regulatory machinery. In the broadest sense, silencing of such genes occurs at three fundamentally different but closely interrelated levels. For example, silencing frequently results from DNA methylation at the site of CpG islands by DNA methyltransferases (DNMT; ref. 2). Silencing can also stem from mutations in chromatin remodeling complexes [i.e., nucleosomal remodeling factors (NURF)] such as SWI/SNF. Finally, silencing can result from multiple post-translational covalent histone modifications, ...
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An Open-label Study in Healthy Male Subjects to Assess the Effect of a Strong CYP3A4 Inhibitor, Ketoconazole, on the...An Open-label Study in Healthy Male Subjects to Assess the Effect of a Strong CYP3A4 Inhibitor, Ketoconazole, on the...
This study investigated the effects of ketoconazole on the pharmacokinetics of refametinib [BAY86-9766; Bayer] in healthy male volunteers. The primary endpoints
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Iron in the structure of Crystal Structure of Sterol 14-Alpha Demethylase (CYP51) From Trypanosoma Brucei in Ligand Free State ...Iron in the structure of Crystal Structure of Sterol 14-Alpha Demethylase (CYP51) From Trypanosoma Brucei in Ligand Free State ...
Mono- and Stereopictres of 5.0 Angstrom coordination sphere of Iron atom in PDB 3g1q: Crystal Structure of Sterol 14-Alpha Demethylase (CYP51) From Trypanosoma Brucei in Ligand Free State
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A novel oligoamine analog inhibitor of histone demethylases blocks colon tumor cell growth in association with histone methylation and gene re-expression. It also markedly potentiates the activity of hypomethylating agents in vitro and in vivo, suggesting that histone demethylase inhibitors may represent a valuable addition to the armamentarium of epigenetic agents. (Clin Cancer Res 2009;15(23):7111-3) ...
Trial for Studying Pharmacokinetic Effects of Ketoconazole on CG100649 - Full Text View - ClinicalTrials.govTrial for Studying Pharmacokinetic Effects of Ketoconazole on CG100649 - Full Text View - ClinicalTrials.gov
study drug CG100649 (1 mg x 6 capsules) will be administered alone on Day 1, or the combination of CG100649 (1 mg x 6 capsules) and Dongkwang ketoconazole tablets (200 mg x 2 tablets) will be administered together on Day 1, followed by additional Dongkwang ketoconazole tablets (200 mg x 2 tablets) which will be administered once a day for 4 days (Days 2-5), for a total of 5 days ...
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RCSB PDB - 5TZ1: Crystal structure of sterol 14-alpha demethylase (CYP51) from Candida albicans in complex with the...RCSB PDB - 5TZ1: Crystal structure of sterol 14-alpha demethylase (CYP51) from Candida albicans in complex with the...
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Lanosterol 14α-demethylase (or CYP51A1) is a cytochrome P450 enzyme that is involved in the conversion of lanosterol to 4,4-dimethylcholesta-8(9),14,24-trien-3β-ol. The cytochrome P450 isoenzymes are a conserved group of proteins that serve as key players in the metabolism of organic substances and the biosynthesis of important steroids, lipids, and vitamins in eukaryotes. As a member of this family, lanosterol 14α-demethylase is responsible for an essential step in the biosynthesis of sterols. In particular, this protein catalyzes the removal of the C-14α-methyl group from lanosterol (Lepesheva et al.). This demethylation step is regarded as the initial checkpoint in the transformation of lanosterol to other sterols that are widely used within the cell (Lepesheva et al.). Although lanosterol 14α-demethylase is present in a wide variety of organisms, this enzyme is studied primarily in the context of fungi, where it plays an essential role in mediating membrane permeability. In fungi, CYP51 ...
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AnatomyOrganismsChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPsychiatry and PsychologyPhenomena and ProcessesDisciplines and OccupationsAnthropology, Education, Sociology and Social PhenomenaTechnology, Industry, AgricultureHumanitiesInformation ScienceHealth Care
14-alpha Demethylase InhibitorsSterol 14-DemethylaseLanosterolHistone DemethylasesJumonji Domain-Containing Histone DemethylasesOxidoreductases, N-DemethylatingAllylamineCandida albicansSterolsAzolesEncyclopedias as TopicCytochrome P-450 Enzyme SystemCholestadienolsDrug Information ServicesNational Library of Medicine (U.S.)Counterfeit DrugsInternetGovernment AgenciesMEDLARSPortal VeinMagnaportheOryza sativaAspergillus oryzaePlant DiseasesFood SupplyFungal ProteinsArchivesAscomycotaBiological Science DisciplinesPeriodicals as TopicPubMedTriticumOrganophosphatesFluconazoleProdrugsInjections, IntravenousArea Under CurveDatabases, FactualAntifungal AgentsDrug Resistance, FungalMicrobial Sensitivity TestsChoice BehaviorDrug RepositioningDrug Resistance, MicrobialFungicides, IndustrialThiophanateCamphor 5-MonooxygenaseCrystallography, X-RayModels, MolecularTrypanosoma brucei bruceiProtein ConformationSleep
Mycosphaerella graminicolaMycosphaerella graminicola
... now relies on the application of azole fungicides which are demethylase inhibitors that inhibit lanosterol 14 alpha-demethylase ... Asci measure 11-14 × 30-40 μm. Ascospores are hyaline, elliptical, and 2.5-4 × 9-16 μm, with two cells of unequal length. ...
ItraconazoleItraconazole
... is pharmacologically distinct from other azole antifungal agents in that it is the only inhibitor in this class ... Absorption of itraconazole is impaired when taken with an antacid, H2 blocker or proton pump inhibitor.[citation needed] ... These distinct activities are unrelated to inhibition of the cytochrome P450 lanosterol 14 alpha-demethylase and the exact ... The clinical formulation is a 1:1:1:1 mixture of four stereoisomers (two enantiomeric pairs). Fluconazole Lanosterol 14α- ...
Lanosterol 14 alpha-demethylaseLanosterol 14 alpha-demethylase
"Mutations in the CYP51 Gene Correlated with Changes in Sensitivity to Sterol 14Alpha-Demethylation Inhibitors in Field Isolates ... "Substrate Preferences and Catalytic Parameters Determined by Structural Characteristics of Sterol 14alpha-demethylase (CYP51) ... "Amino Acid Substitutions in the Cytochrome P-450 Lanosterol 14Alpha-Demethylase (CYP51A1) from Azole-resistant Candida albicans ... The effectiveness of imidazoles and triazoles (common azole subclasses) as inhibitors of 14α-demethylase have been confirmed ...
Lanosterol 14 alpha-demethylaseLanosterol 14 alpha-demethylase
... effects of P45014DM inhibitors on sterol biosynthesis downstream of lanosterol". Journal of Lipid Research. 32 (6): 893-902. ... "Sterol 14alpha-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms". Biochimica et Biophysica Acta. 1770 (3 ... "Amino acid substitutions in the cytochrome P-450 lanosterol 14alpha-demethylase (CYP51A1) from azole-resistant Candida albicans ... "Substrate preferences and catalytic parameters determined by structural characteristics of sterol 14alpha-demethylase (CYP51) ...
Active siteActive site
For example, the competitive enzyme inhibitor methylglucoside can bind tightly to the active site of 4-alpha-glucanotransferase ... 8 Inhibitors. *9 Examples of competitive and irreversible enzyme inhibitors *9.1 Competitive inhibitor: HIV protease inhibitor ... Competitive reversible inhibitor. HIV protease inhibitors. Yes. Yes Non-competitive reversible inhibitor. Heavy metals such as ... Examples of competitive and irreversible enzyme inhibitorsEdit. Competitive inhibitor: HIV protease inhibitorEdit. ...
IsavuconazoniumIsavuconazonium
Inducers result in levels of isavuconazole that are too low and won't work, and inhibitors can cause high levels of ... Isavuconazole works by inhibiting lanosterol 14 alpha-demethylase, the enzyme responsible for converting lanosterol to ...
KetoconazoleKetoconazole
... shampoo in conjunction with an oral 5α-reductase inhibitor has been used off label to treat androgenic alopecia. ... Both isomers were relatively weak inhibitors of human placental aromatase. Resistance to ketoconazole has been observed in a ... Defects in the sterol 5-6 desaturase enzyme reduce the toxic effects of azole inhibition of the 14-alpha demethylation step. ... 624-. ISBN 978-0-7817-8355-2. J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and ...
Chromosome 11 (human)Chromosome 11 (human)
Srp receptor alpha subunit TAF1D: TATA box binding protein associated factor RNA polymerase 1 subunit D TALDO1 encoding protein ... ribonuclease inhibitor 1 RNU2-2: encoding protein RNA, U2 small nuclear 2 ROM1: retinal outer segment membrane protein 1 RPL27A ... lysine demethylase 2A KIAA1549L encoding protein KIAA1549-like LPXN: leupaxin LRFN4 encoding protein Leucine rich repeat and ... encoding protein Apoptosis inhibitor 5 APLNR: Apelin receptor (APJ receptor) APOA4: apolipoprotein A-IV ARCN1 encoding protein ...
Chromosome 7 (human)Chromosome 7 (human)
... encoding protein Lysine demethylase 7A LRRC17: leucine-rich repeat containing protein 17 LSM5: U6 small nuclear RNA and mRNA ... inhibitor of growth protein 3 INTS1: encoding protein Integrator complex subunit 1 IQCE: IQ domain-containing protein E KDM7A: ... encoding enzyme Alpha-aminoadipic semialdehyde synthase, mitochondrial ARHGEF35: encoding protein Rho guanine nucleotide ... 2014-05-14]. Pertea M, Salzberg SL (2010). "Between a chicken and a grape: estimating the number of human genes". Genome Biol. ...
Steroidogenesis inhibitorSteroidogenesis inhibitor
"Inhibitors of sterol synthesis. Metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one after intravenous administration to ... A steroidogenesis inhibitor, also known as a steroid biosynthesis inhibitor, is a type of drug which inhibits one or more of ... 7-DHCR inhibitors produce symptoms in animals similar to those seen SLOS, and as such, like 24-DHCR inhibitors (see below), are ... Steroidogenic enzyme Neurosteroidogenesis inhibitor Vanden Bossche H (1992). "Inhibitors of P450-dependent steroid biosynthesis ...
Gilead SciencesGilead Sciences
This acquisition gave Gilead first-in-class small molecule inhibitors of histone demethylases involved in regulating gene ... Ioannis Stamatopoulos (2017-02-12). "Pharma M&A In 2017: The Most Likely Deal Hunters". Seeking Alpha. Retrieved 2017-03-12. ... for $400 million, giving Gilead control of the compound NDI-010976 (an ACC inhibitor) and other preclinical ACC inhibitors for ... The acquisition brings drug candidate CYT387, an orally-administered, once-daily, selective inhibitor of the Janus kinase (JAK ...
Chromatin remodelingChromatin remodeling
HDAC inhibitors can induce p21 (WAF1) expression, a regulator of p53's tumor suppressoractivity. HDACs are involved in the ... Benevolenskaya EV (August 2007). "Histone H3K4 demethylases are essential in development and differentiation". Biochemistry and ... factor implicated in the tumorigenesis and progression of breast cancer via its binding to the estrogen receptor alpha (ERα). ... Hence, strategies are now being tried to overcome epigenetic silencing with synergistic combination of HDAC inhibitors or HDI ...
PELP-1PELP-1
... of histone H3 methylation that facilitates oestrogen receptor-alpha target gene activation by regulating lysine demethylase 1 ... Recent studies described an inhibitor (D2) that block PELP1 interactions with AR. Since PELP1 interacts with histone ... ERR-alpha, PR, GR, AR, and RXR. PELP1 also functions as a coregulator of several other transcription factors, including AP1, ... lysine-specific demethylase 1 (KDM1), PRMT6, and CARM1. PELP1 also interacts with cell cycle regulators such as pRb. E2F1, and ...
2-oxoglutarate (2OG)-dependent dioxygenases2-oxoglutarate (2OG)-dependent dioxygenases
... inhibitors. Inhibitors that compete against the substrate were also developed, such as peptidyl-based inhibitors that target ... Walport LJ, Hopkinson RJ, Schofield CJ (December 2012). "Mechanisms of human histone and nucleic acid demethylases". Curr. Opin ... "Direct detection of oxygen intermediates in the non-heme Fe enzyme taurine/alpha-ketoglutarate dioxygenase". J. Am. Chem. Soc. ... The inhibitors that were regularly used to target 2OG-dependent dioxygenase include N-oxalylglycine (NOG), pyridine-2,4- ...
ReelinReelin
DNMT1 inhibitors in animals have been shown to increase the expression of both reelin and GAD67, and both DNMT inhibitors and ... as demethylases open up the RELN gene. The activation of dendrite growth by reelin is apparently conducted through Src family ... a site distinct from the region of reelin shown to associate with VLDLR/ApoER2 binds to the alpha-3-beta-1 integrin receptor. ... Methylation inhibitors and histone deacetylase inhibitors, such as valproic acid, increase reelin mRNA levels, while L- ...
Epigenetics of neurodegenerative diseasesEpigenetics of neurodegenerative diseases
DNA methyltransferase inhibitors, and histone demethylase inhibitors.[6][7] The majority of epigenetic drugs tested for use ... In an alpha-synuclein overexpressing Drosophila model of PD, vorinostat (as well as sodium butyrate) reduced alpha-synuclein- ... HDAC inhibitor (small molecule) benzamide M344 MC 19 fatty acid Sodium butyrate M (y) 5, 6, 7 ; H (ny) D (y) 11 M (y) 14; R (y ... "Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease". primary. Science. 317 (5837): ...
Christopher J. SchofieldChristopher J. Schofield
"Pan-Histone Demethylase Inhibitors Simultaneously Targeting Jumonji C and Lysine-Specific Demethylases Display High Anticancer ... l-alpha-aminoadipoyl)-l-cysteinyl-d-alpha-aminobutyrate". Biochemical Journal. 372 (3): 687-693. doi:10.1042/bj20021627. ISSN ... "A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response". Nature. 488 (7411): 404-408 ... The histone demethylases are of interest both with respect to their links to diseases, including cancer and inflammatory ...
Cytochrome P450Cytochrome P450
7-alpha hydroxylation of 24-hydroxycholesterol. 1 subfamily, 1 gene. CYP39A1 CYP46. cholesterol 24-hydroxylase. 1 subfamily, 1 ... Inhibitors and certain substrates that bind directly to the heme iron give rise to the type II difference spectrum, with a ... steroid biosynthesis, 17-alpha hydroxylase. 1 subfamily, 1 gene. CYP17A1 CYP19. steroid biosynthesis: aromatase synthesizes ... CYP27A1 (bile acid biosynthesis), CYP27B1 (vitamin D3 1-alpha hydroxylase, activates vitamin D3), CYP27C1 (unknown function) ...
MeldoniumMeldonium
Potential Clinical Advantages of Tight Binding Inhibitors [Chapter 7, §7.8]". Evaluation of Enzyme Inhibitors in Drug Discovery ... Meldonium has also been found to induce anticonvulsant and antihypnotic effects involving alpha 2-adrenergic receptors as well ... akin to the action of histone demethylases), dimethylamine, and (1-methylimidazolidin-4-yl)acetic acid, "an unexpected product ... high affinity of …tight binding inhibitors allows one to minimize the dose of drug to which patients are exposed, thus limiting ...
EpigeneticsEpigenetics
Histones H3 and H4 can also be manipulated through demethylation using histone lysine demethylase (KDM). This recently ... "Soy isoflavone supplementation in healthy men prevents NF-kappa B activation by TNF-alpha in blood lymphocytes". Free Radic. ... "The histone methyltransferase inhibitor BIX01294 enhances the cardiac potential of bone marrow cells.". Stem Cells Dev. 22: ... 14 (2): 159-66. PMID 16391557. doi:10.1038/sj.ejhg.5201538.. Robert Winston refers to this study in a lecture; see also ...
Chromosome 16Chromosome 16
HBAP1: Hemoglobin, alpha pseudogene 1. *HBHR, ATR1: Alpha-thalassemia/mental retardation syndrome, type 1 ... KDM8: encoding protein Lysine demethylase 8. *LINC00273 encoding protein Long intergenic non-protein coding RNA 273 ... CIAPIN1: Anamorsin (originally, Cytokine induced apoptosis inhibitor 1). *CKLF: Chemokine-like factor ... G-banding patterns of human chromosome 16 in three different resolutions (400,[14] 550[15] and 850[4]). Band length in this ...
Stress granuleStress granule
Tsai WC, Reineke LC, Jain A, Jung SY, Lloyd RE (September 2017). "Histone arginine demethylase JMJD6 is linked to stress ... Mahboubi H, Barisé R, Stochaj U (July 2015). "5'-AMP-activated protein kinase alpha regulates stress granule biogenesis". ... "Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin to control growth and ... "Pur-alpha functionally interacts with FUS carrying ALS-associated mutations". Cell Death & Disease. 6: e1943. doi:10.1038/cddis ...
L-lysine 6-monooxygenase (NADPH)L-lysine 6-monooxygenase (NADPH)
Cholesterol 7 alpha-hydroxylase. *Methane monooxygenase. *3A4. *Lanosterol 14 alpha-demethylase. *24-hydroxycholesterol 7α- ...
PHF8PHF8
histone demethylase activity (H3-K9 specific). • histone demethylase activity (H4-K20 specific). • chromatin binding. • ... PHF8 belongs to the family of ferrous iron and alpha-ketoglutarate-dependent hydroxylases superfamily.,[6] and is active as a ... histone demethylase activity (H3-K36 specific). • oxidoreductase activity. • histone demethylase activity (H3-K27 specific). • ... histone demethylase activity. • zinc ion binding. Cellular component. • nuclear membrane. • nucleoplasm. • nucleolus. • cell ...
Tyrosine hydroxylaseTyrosine hydroxylase
Older examples of inhibitors mentioned in the literature include oudenone[45] and aquayamycin.[46] ... At the carboxyl terminal of the peptide chain there's a short alpha helix domain that allows tetramerization.[15] The central ~ ... Ono M, Okamoto M, Kawabe N, Umezawa H, Takeuchi T (Mar 1971). "Oudenone, a novel tyrosine hydroxylase inhibitor from microbial ... 24 (14): 3389-94. doi:10.1021/bi00335a001. PMID 2412578.. *^ Grenett HE, Ledley FD, Reed LL, Woo SL (Aug 1987). "Full-length ...
DNA methyltransferaseDNA methyltransferase
DNMT inhibitors[edit]. Because of the epigenetic effects of the DNMT family, some DNMT inhibitors are under investigation for ... hsdM contains an alpha-helical domain at the N-terminus, the HsdM N-terminal domain.[7] ... Svedruzić ZM (2008). "Mammalian cytosine DNA methyltransferase Dnmt1: enzymatic mechanism, novel mechanism-based inhibitors, ... which is formed by 4 small beta-sheets and 8 alpha-helices. The N- and C-terminal domains form a cleft that accommodates the ...
AnatomyOrganismsChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPsychiatry and PsychologyPhenomena and ProcessesDisciplines and OccupationsAnthropology, Education, Sociology and Social PhenomenaTechnology, Industry, AgricultureHumanitiesInformation ScienceHealth Care
14-alpha Demethylase InhibitorsSterol 14-DemethylaseLanosterolHistone DemethylasesJumonji Domain-Containing Histone DemethylasesOxidoreductases, N-DemethylatingAllylamineCandida albicansSterolsAzolesEncyclopedias as TopicCytochrome P-450 Enzyme SystemCholestadienolsDrug Information ServicesNational Library of Medicine (U.S.)Counterfeit DrugsInternetGovernment AgenciesMEDLARSPortal VeinMagnaportheOryza sativaAspergillus oryzaePlant DiseasesFood SupplyFungal ProteinsArchivesAscomycotaBiological Science DisciplinesPeriodicals as TopicPubMedTriticumOrganophosphatesFluconazoleProdrugsInjections, IntravenousArea Under CurveDatabases, FactualAntifungal AgentsDrug Resistance, FungalMicrobial Sensitivity TestsChoice BehaviorDrug RepositioningDrug Resistance, MicrobialFungicides, IndustrialThiophanateCamphor 5-MonooxygenaseCrystallography, X-RayModels, MolecularTrypanosoma brucei bruceiProtein ConformationSleep
A mutation in the 14 alpha-demethylase gene of Uncinula necator that correlates with resistance to a sterol biosynthesis...A mutation in the 14 alpha-demethylase gene of Uncinula necator that correlates with resistance to a sterol biosynthesis...
A mutation in the 14 alpha-demethylase gene of Uncinula necator that correlates with resistance to a sterol biosynthesis ... The gene encoding the target of DMIs (eburicol 14 alpha-demethylase) from five sensitive and seven resistant isolates was ... A mutation in the 14 alpha-demethylase gene of Uncinula necator that correlates with resistance to a sterol biosynthesis ... inhibitor.. C Délye, F Laigret, M F Corio-Costet. Applied and Environmental Microbiology Aug 1997, 63 (8) 2966-2970; DOI: ...
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RCSB PDB - 5TZ1: Crystal structure of sterol 14-alpha demethylase (CYP51) from Candida albicans in complex with the...RCSB PDB - 5TZ1: Crystal structure of sterol 14-alpha demethylase (CYP51) from Candida albicans in complex with the...
Structural analyses of Candida albicans sterol 14 alpha-demethylase complexed with azole drugs address the molecular basis of ... Classification: OXIDOREDUCTASE / OXIDOREDUCTASE INHIBITOR * Deposited: 2016-11-21 Released: 2017-03-15 ... Sterol 14-alpha demethylase A, B 490 Candida albicans EC#: 1.14.13.70 IUBMB Mutation: A48P, S263L Gene Name(s): ERG11 CYP51 ... Crystal structure of sterol 14-alpha demethylase (CYP51) from Candida albicans in complex with the tetrazole-based antifungal ...
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RCSB PDB - 4ZE0: Saccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) Y140F mutant complexed with VoriconazoleRCSB PDB - 4ZE0: Saccharomyces cerevisiae CYP51 (Lanosterol 14-alpha demethylase) Y140F mutant complexed with Voriconazole
Classification: oxidoreductase/oxidoreducatse inhibitor. *Organism(s): Saccharomyces cerevisiae (strain YJM789). *Expression ... C16 H14 F3 N5 O. BCEHBSKCWLPMDN-MGPLVRAMSA-N. Ligand Interaction. ... Triazole resistance can arise due to single mutations in the drug target lanosterol 14α-demethylase (Erg11p/CYP51). We have ... Triazole resistance can arise due to single mutations in the drug target lanosterol 14α-demethylase (Erg11p/CYP51). We have ...
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Lanosterol 14 alpha-demethylase - WikipediaLanosterol 14 alpha-demethylase - Wikipedia
... effects of P45014DM inhibitors on sterol biosynthesis downstream of lanosterol". Journal of Lipid Research. 32 (6): 893-902. ... "Sterol 14alpha-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms". Biochimica et Biophysica Acta. 1770 (3 ... "Amino acid substitutions in the cytochrome P-450 lanosterol 14alpha-demethylase (CYP51A1) from azole-resistant Candida albicans ... "Substrate preferences and catalytic parameters determined by structural characteristics of sterol 14alpha-demethylase (CYP51) ...
en.wikipedia.org
A Drug-Drug Interaction Study of Ketoconazole, Rifampicin and Ritonavir-Boosted Atazanavir With Single-Dose RO5093151 in...A Drug-Drug Interaction Study of Ketoconazole, Rifampicin and Ritonavir-Boosted Atazanavir With Single-Dose RO5093151 in...
HIV Protease Inhibitors. Protease Inhibitors. Enzyme Inhibitors. Molecular Mechanisms of Pharmacological Action. Anti-HIV ... Cytochrome P-450 CYP3A Inhibitors. Cytochrome P-450 Enzyme Inhibitors. Antifungal Agents. 14-alpha Demethylase Inhibitors. ... Nucleic Acid Synthesis Inhibitors. Cytochrome P-450 CYP2B6 Inducers. Cytochrome P-450 Enzyme Inducers. Cytochrome P-450 CYP2C8 ... Steroid Synthesis Inhibitors. Hormone Antagonists. Hormones, Hormone Substitutes, and Hormone Antagonists. Physiological ...
clinicaltrials.gov
An Open Study of the Effect of Itraconazole Oral Solution for the Treatment of Fluconazole Refractory Oropharyngeal Candidiasis...An Open Study of the Effect of Itraconazole Oral Solution for the Treatment of Fluconazole Refractory Oropharyngeal Candidiasis...
Cytochrome P-450 CYP3A Inhibitors. Cytochrome P-450 CYP2C9 Inhibitors. Cytochrome P-450 CYP2C19 Inhibitors. ... Enzyme Inhibitors. Molecular Mechanisms of Pharmacological Action. Steroid Synthesis Inhibitors. Hormone Antagonists. Hormones ... Patients who relapse during follow-up are re-treated for 14-28 days; if lesions clear, patients may enter the maintenance ... 14-alpha Demethylase Inhibitors. Cytochrome P-450 Enzyme Inhibitors. ...
clinicaltrials.gov
Reduction of EArly mortaLITY in HIV-infected Adults and Children Starting Antiretroviral Therapy - Full Text View -...Reduction of EArly mortaLITY in HIV-infected Adults and Children Starting Antiretroviral Therapy - Full Text View -...
HIV Integrase Inhibitors. Integrase Inhibitors. Enzyme Inhibitors. Molecular Mechanisms of Pharmacological Action. Antifungal ... Cytochrome P-450 Enzyme Inhibitors. Steroid Synthesis Inhibitors. Hormone Antagonists. Hormones, Hormone Substitutes, and ... Contraindications to any proposed antiretroviral drugs (including integrase inhibitors), isoniazid, fluconazole, albendazole or ...
clinicaltrials.gov
A Drug-Drug Interaction Study of the Effect of Rabeprazole, Itraconazole or Fluconazole on the Pharmacokinetics of Vismodegib -...A Drug-Drug Interaction Study of the Effect of Rabeprazole, Itraconazole or Fluconazole on the Pharmacokinetics of Vismodegib -...
Proton Pump Inhibitors. Cytochrome P-450 CYP2C9 Inhibitors. Cytochrome P-450 CYP2C19 Inhibitors. ... A Clinical Drug-Drug Interaction Study to Evaluate the Effect of a Proton Pump Inhibitor, a Combined P-gp/CYP3A4 Inhibitor, and ... Enzyme Inhibitors. Molecular Mechanisms of Pharmacological Action. Steroid Synthesis Inhibitors. Hormone Antagonists. Hormones ... an inhibitor of P-glycoprotein and CYP3A4, or an inhibitor of CYP2C9 on the pharmacokinetics of vismodegib in healthy female ...
clinicaltrials.gov
Lanosterol 14 alpha-demethylase - WikipediaLanosterol 14 alpha-demethylase - Wikipedia
"Mutations in the CYP51 Gene Correlated with Changes in Sensitivity to Sterol 14Alpha-Demethylation Inhibitors in Field Isolates ... "Substrate Preferences and Catalytic Parameters Determined by Structural Characteristics of Sterol 14alpha-demethylase (CYP51) ... "Amino Acid Substitutions in the Cytochrome P-450 Lanosterol 14Alpha-Demethylase (CYP51A1) from Azole-resistant Candida albicans ... The effectiveness of imidazoles and triazoles (common azole subclasses) as inhibitors of 14α-demethylase have been confirmed ...
en.wikipedia.org
Synthesis, Molecular Docking Studies, and Antifungal Activity Evaluation of New Benzimidazole-Triazoles as Potential Lanosterol...Synthesis, Molecular Docking Studies, and Antifungal Activity Evaluation of New Benzimidazole-Triazoles as Potential Lanosterol...
... α-Demethylase Inhibitors. Nafiz Öncü Can,1,2 Ulviye Acar Çevik,2,3 Begüm Nurpelin Sağlık,2,3 Serkan Levent,2,3 Büşra Korkut,4 ... α-demethylase inhibitors," Journal of Receptors and Signal Transduction, vol. 33, no. 4, pp. 234-243, 2013. View at Publisher ... α-demethylase inhibitors," International Journal of Molecular Sciences, vol. 18, no. 1, article no. 177, 2017. View at ... α-demethylase inhibitors: Synthesis, antifungal activity and docking study," Journal of Enzyme Inhibition and Medicinal ...
hindawi.com
ERG11 - Lanosterol 14-alpha demethylase - Candida glabrata (strain ATCC 2001 / CBS 138 / JCM 3761 / NBRC 0622 / NRRL Y-65) ...ERG11 - Lanosterol 14-alpha demethylase - Candida glabrata (strain ATCC 2001 / CBS 138 / JCM 3761 / NBRC 0622 / NRRL Y-65) ...
It transforms lanosterol into 4,4-dimethyl cholesta-8,14,24-triene-3-beta-ol (By similarity). ... anti-sense experiments and use of specific protein inhibitors.,/p> ,p>More information in the ,a href="http://geneontology.org/ ... "In vitro and in vivo effects of 14alpha-demethylase (ERG11) depletion in Candida glabrata.". Nakayama H., Nakayama N., Arisawa ... 14. Turni. 349 - 353. Combined sources. Manual assertion inferred from combination of experimental and computational evidencei ...
uniprot.org
Drug Information Portal - U.S. National Library of Medicine - Quick Access to Quality Drug InformationDrug Information Portal - U.S. National Library of Medicine - Quick Access to Quality Drug Information
Compared to other azole antifungals, posaconazole is a significantly more potent inhibitor of sterol 14-alpha demethylase. ... Inhibition of 14-alpha-demethylase prevents the conversion of lanosterol to ergosterol, an important component of the fungal ... Posaconazole strongly inhibits 14-alpha demethylase, a cytochrome P450-dependent enzyme. ...
druginfo.nlm.nih.gov
Biochemical and structural characterization of CYP124: A methyl-branched lipid ω-hydroxylase from Mycobacterium tuberculosis |...Biochemical and structural characterization of CYP124: A methyl-branched lipid ω-hydroxylase from Mycobacterium tuberculosis |...
2001) Crystal structure of cytochrome P450 14alpha-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with ... The enzymatic specificity and structures reported here provide a scaffold for the design and testing of specific inhibitors of ... 1978) Measurement of substrate and inhibitor binding to microsomal cytochrome P-450 by optical-difference spectroscopy. Methods ... 2006) Biophysical characterization of the sterol demethylase P450 from Mycobacterium tuberculosis, its cognate ferredoxin, and ...
pnas.org
Mycosphaerella graminicola - WikipediaMycosphaerella graminicola - Wikipedia
... now relies on the application of azole fungicides which are demethylase inhibitors that inhibit lanosterol 14 alpha-demethylase ... Asci measure 11-14 × 30-40 μm. Ascospores are hyaline, elliptical, and 2.5-4 × 9-16 μm, with two cells of unequal length. ...
en.wikipedia.org
Past, Present, and Future of Antifungal Drug Development | Springer for Research & DevelopmentPast, Present, and Future of Antifungal Drug Development | Springer for Research & Development
1-(o-Chloro-alpha,alpha-diphenyl benzyl)imidazole (clotrimazole) is a white crystalline solid that is sparingly soluble in ... 5-FU is a specific inhibitor of an enzyme essential for DNA synthesis namely thymidylate synthetase. This antifungal is ... Design and synthesis of novel triazole antifungal derivatives based on the active site of fungal lanosterol 14a-demethylase ( ... Therefore efforts focused on the discovery of useful inhibitors of fungal specific, chitin, cell wall glucan and mannoprotein ...
rd.springer.com
Diflucan (fluconazole) dosing, indications, interactions, adverse effects, and moreDiflucan (fluconazole) dosing, indications, interactions, adverse effects, and more
Highly selective inhibitor of fungal cytochrome P-450-dependent enzyme lanosterol 14-alpha-demethylase ... Subsequent loss of normal sterols correlates with accumulation of 14 alpha-methyl sterols in fungi and may be responsible for ... Recurrent: 150 mg PO qDay for 10-14 days followed by 150 mg once weekly for 6 months ...
reference.medscape.com
A Novel ATP-Binding Cassette Transporter Involved in Multidrug Resistance in the Phytopathogenic FungusPenicillium digitatum |...A Novel ATP-Binding Cassette Transporter Involved in Multidrug Resistance in the Phytopathogenic FungusPenicillium digitatum |...
Inhibitors of energy-dependent efflux of fungicide fenarimol by Aspergillus nidulans. Exp. Mycol. 11 1987 1 10 ... Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes ... Sterol demethylation inhibitors (DMIs) have a common site of action within the fungal sterol biosynthesis pathway, which is the ... Demethylation inhibitor (DMI)-resistant strains of the plant pathogenic fungus Penicillium digitatum were shown to be ...
aem.asm.org
Frontiers | Accumulation of Azole Drugs in the Fungal Plant Pathogen Magnaporthe oryzae Is the Result of Facilitated Diffusion...Frontiers | Accumulation of Azole Drugs in the Fungal Plant Pathogen Magnaporthe oryzae Is the Result of Facilitated Diffusion...
2011). A sterol 14alpha-demethylase is required for conidiation, virulence and for mediating sensitivity to sterol ... 2012). The monoamine oxidase A inhibitor clorgyline is a broad-spectrum inhibitor of fungal ABC and MFS transporter efflux pump ... Lepesheva, G. I., and Waterman, M. R. (2007). Sterol 14alpha-demethylase cytochrome P450 (CYP51), a P450 in all biological ... Heterologous expression of mutated eburicol 14alpha-demethylase (CYP51) proteins of Mycosphaerella graminicola to assess ...
frontiersin.org
Antley Bixler syndrome | Genetic and Rare Diseases Information Center (GARD) - an NCATS ProgramAntley Bixler syndrome | Genetic and Rare Diseases Information Center (GARD) - an NCATS Program
A similar clinical picture is observed in patients exposed in utero to fluconazole, a lanosterol 14 alpha-demethylase inhibitor ...
rarediseases.info.nih.gov
The EPA National Library Catalog | EPA National Library Network | US EPAThe EPA National Library Catalog | EPA National Library Network | US EPA
... an inhibitor of the cytochrome P-450 (P-450) enzyme lanosterol 14 alpha-demethylase. Two plasmids were isolated which ...
cfpub.epa.gov
Small-Molecule Inhibitors Targeting Sterol 14α-Demethylase (CYP51): Synthesis, Molecular Modelling and Evaluation Against...Small-Molecule Inhibitors Targeting Sterol 14α-Demethylase (CYP51): Synthesis, Molecular Modelling and Evaluation Against...
Characteristics of the heterologously expressed human lanosterol 14alpha-demethylase (other names: P45014DM, CYP51, P45051) and ... Small-Molecule Inhibitors Targeting Sterol 14α-Demethylase (CYP51): Synthesis, Molecular Modelling and Evaluation Against ... papers/small-molecule-inhibitors-targeting-sterol-14-deme/32459374. ... Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole- ...
meta.org
Molecular Modelling of the Emergence of Azole Resistance in Mycosphaerella graminicolaMolecular Modelling of the Emergence of Azole Resistance in Mycosphaerella graminicola
Control of the pathogen now relies on the application of azole fungicides which are demethylase inhibitors (DMIs) that inhibit ... PCR cloning and detection of point mutations in the eburicol 14alpha-demethylase (CYP51) gene from Erysiphe graminis f. sp. ... Cloning and sequence analysis of the eburicol 14alpha-demethylase gene of the obligate biotrophic grape powdery mildew fungus. ... Contribution of mutations in the cytochrome P450 14alpha-demethylase (Erg11p, Cyp51p) to azole resistance in Candida albicans. ...
pubmedcentralcanada.ca
Avasimibe | P450 (e.g. CYP17) inhibitor | Read Reviews & Product Use Citations Avasimibe | P450 (e.g. CYP17) inhibitor | Read Reviews & Product Use Citations
... cholesterol acyltransferase inhibitor with IC50 of 2.9, 13.9, 26.5 μM for CYP2C9, CYP1A2, and CYP2C19 Find all the information ... U73122 is a potent phospholipase C (PLC) inhibitor, which reduces agonist-induced Ca2+ increases in platelets and PMN. ... Abiraterone Acetate is an acetate salt form of Abiraterone which is a steroidal cytochrome CYP17 inhibitor with IC50 of 72 nM ... 3] Avasimibe inhibits ACTC with IC50 of 3.3 μM in IC-21 macrophages with consideration of the total inhibitor concentration in ...
selleckchem.com
Pfizer Licensed ProductsPfizer Licensed Products
PF-04691502 is an ATP-competitive PI3K(α/β/δ/γ)/mTOR dual inhibitor with Ki of 1.8 nM/2.1 nM/1.6 nM/1.9 nM and 16 nM in cell- ... Prazosin HCl is a competitive alpha-1 adrenoceptor antagonist, used to treat high blood pressure or benign prostatic ... PF-04691502 is an ATP-competitive PI3K(α/β/δ/γ)/mTOR dual inhibitor with Ki of 1.8 nM/2.1 nM/1.6 nM/1.9 nM and 16 nM in cell- ... PF-4708671 is a cell-permeable inhibitor of p70 ribosomal S6 kinase (S6K1 isoform) with Ki/IC50 of 20 nM/160 nM in cell-free ...
selleckchem.com
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Mediated by lanosterolAzoleErgosterolPotentInhibit lanosterol 14-alpha-demethylaseAntifungalCytochrome P-4KetoconazoleFluconazoleDMIsInhibitionSynthesisP450CYP3A4SterolsOrganismVoriconazoleCYP51A1CYP17Enzyme InhibitorsInhibitsSmall MoleculeProteinHistoneCorrelates2018IC50DemethylationSystemicTrypanosomaProtease InhibitorMutationMechanismFungal InfectionBiosynthesis2020FungiResistanceMRNAAromataseKinase
Mediated by lanosterol1
Azole6
Ergosterol6
Potent16
Inhibit lanosterol 14-alpha-demethylase2
Antifungal1
  • Echinocandins or glucan fusion inhibitors (eg, caspo- fungin) are a new category of antifungal drugs that disorganize fun- FUNGAL INFECTIONS gal cell walls sort of than fungal cell membranes. (nippon-kan.org)
Cytochrome P-41
Ketoconazole2
Fluconazole2
DMIs2
Inhibition5
Synthesis2
P4504
CYP3A41
  • This randomized, open-label, 4-arm, multiple-dose study will evaluate the effect of coadministration of a protein pump inhibitor, an inhibitor of P-glycoprotein and CYP3A4, or an inhibitor of CYP2C9 on the pharmacokinetics of vismodegib in healthy female subjects of non-childbearing potential. (clinicaltrials.gov)
Sterols2
Organism1
  • Although the structure of 14α-demethylase may vary substantially from one organism to the next, sequence alignment analysis reveals that there are six regions in the protein that are highly conserved in eukaryotes . (wikipedia.org)
Voriconazole1
CYP51A11
CYP171
Enzyme Inhibitors1
Inhibits2
  • Avasimibe inhibits ACTC with IC50 of 3.3 μM in IC-21 macrophages with consideration of the total inhibitor concentration in the assay sample. (selleckchem.com)
  • Sunitinib Malate is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM in cell-free assays, and also inhibits c-Kit. (selleckchem.com)
Small Molecule2
  • Based on its potential as a cancer target, a number of small molecule inhibitors have been developed to specifically inhibit mutant forms of IDH (mIDH1 and mIDH2). (nature.com)
  • Viamet, in collaboration with Therapeutics for Rare and Neglected diseases, is investigating VT-1129, a small-molecule lanosterol demethylase inhibitor, developed using the company's Metallophile technology, for treating fungal infections, including Cryptococcus neoformans meningitis. (drugapprovalsint.com)
Protein4
  • In particular, this protein catalyzes the removal of the C-14α- methyl group from lanosterol . (wikipedia.org)
  • Homology modeling reveals that substrates migrate from the surface of the protein to the enzyme's buried active site through a channel that is formed in part by the A' alpha helix and the β4 loop. (wikipedia.org)
  • PFI-1 is a highly selective BET (bromodomain-containing protein) inhibitor for BRD4 with IC50 of 0.22 μM and for BRD2 with IC50 of 98 nM in a cell-free assay. (selleckchem.com)
  • ATAJ2892 AJ002892 678bp RNA PLN 14-NOV-1997 Arabidopsis thaliana mRNA for glycine-rich RNA-binding protein (AtGRP2). (bio.net)
Histone5
Correlates1
20181
IC5010
Demethylation3
  • Demethylation inhibitor (DMI)-resistant strains of the plant pathogenic fungus Penicillium digitatum were shown to be simultaneously resistant to cycloheximide, 4-nitroquinoline- N -oxide (4NQO), and acriflavine. (asm.org)
  • Demethylation inhibitor (DMI) fungicides have been relied upon heavily to manage this disease. (eurekamag.com)
  • Frequency of C. beticola populations resistant to Quinone outside inhibitors (QoI) was 81% (51/63 isolates), 98% (62/63) to sterol-demethylation inbibitors (DMI) and 54% (34/63) to methyl-2-benzimidazole carbamate fungicides (MBC). (springer.com)
Systemic1
  • A CYP3A inhibitor used to increase the systemic exposure of atazanavir or darunavir in combination with other antiretroviral agents in the treatment of HIV-1 infection. (drugbank.ca)
Trypanosoma1
  • In this study, the authors solved 1.9 Å resolution crystal structures of 14DM from Trypanosoma brucei in both a native state and in a complex with the inhibitor VN1. (asbmb.org)
Protease Inhibitor9
  • An HIV protease inhibitor used in combination with other antiretroviral agents for the treatment of HIV-1 with advanced immunodeficiency. (drugbank.ca)
  • A HIV protease inhibitor used in the treatment of human immunodeficiency virus (HIV) infection in patients with history of prior antiretroviral therapies. (drugbank.ca)
  • An NS3/4A viral protease inhibitor used in combination with other antivirals for the curative treatment of chronic Hepatitis C Virus infections. (drugbank.ca)
  • A protease inhibitor used to treat HIV-1 resistant to more than 1 protease inhibitor. (drugbank.ca)
  • An antiviral protease inhibitor used in combination with other antiretrovirals for the treatment of HIV. (drugbank.ca)
  • An HIV-1 protease inhibitor used in combination with ritonavir to treat human immunodeficiency virus (HIV). (drugbank.ca)
  • A protease inhibitor used to treat HIV infection. (drugbank.ca)
  • A hepatitis C virus NS3/4A protease inhibitor used in combination with other medications to treat chronic hepatitis C genotype 1 infection. (drugbank.ca)
  • A viral protease inhibitor used in the treatment of HIV infection. (drugbank.ca)
Mutation1
  • Many of these inhibitors are in clinical trials for patients with AML or solid tumors demonstrating the rapid advancement from the first report of the IDH1 mutation seven years ago to current late phase clinical trials. (nature.com)
Mechanism1
Fungal Infection1
Biosynthesis1
20202
  • Send us your comments by March 14, 2020. (clinicaltrials.gov)
  • 3.3.1, une solution de gestion de contenu sous licence GNU GPL Le DHU 2020 s'efforce d'assurer au mieux de ses possibilités, l'exactitude des informations diffusées, au moment de leur mise en ligne sur le site, mais n'en garantit en aucune façon l'exactitude, la précision ou l'exhaustivité. (levitra8norx.com)
Fungi1
Resistance3
MRNA2
  • AB008782 AB008782 2235bp mRNA PLN 14-NOV-1997 Arabidopsis thaliana mRNA for sulfate transporter, complete cds. (bio.net)
  • ATFERROCH Y13156 1797bp RNA PLN 14-NOV-1997 Arabidopsis thaliana mRNA for ferrochelatase. (bio.net)
Aromatase2
Kinase3
  • An antineoplastic kinase inhibitor used to treat chronic lymphocytic leukemia (CLL), relapsed follicular B-cell non-Hodgkin lymphoma (FL), and relapsed small lymphocytic lymphoma (SLL). (drugbank.ca)
  • A kinase inhibitor used for the chronic phase treatment of Chronic Myeloid Leukemia (CML) that is Philadelphia chromosome positive and for the treatment of CML that is resistant to therapy containing imatinib. (drugbank.ca)
  • A kinase inhibitor used to treat HR+, HER2- advanced or metastatic breast cancer. (drugbank.ca)