Clotrimazole
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Basic Info
| Common Name | Clotrimazole(F04743) |
| 2D Structure | |
| Description | Clotrimazole is an imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. There is the potential for drug interactions with Clotrimazole if taken orally, as it is a potent, specific inhibitor of cytochrome P450 oxidase enzymes and so may alter the metabolism of other drugs. Clotrimazole is an antifungal medication commonly used in the treatment of fungal infections of both humans and animals such as vaginal yeast infections and ringworm. An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. Clotrimazole is a potent, specific inhibitor of cytochrome P450 oxidase enzymes. Hence, it may alter the metabolism of other drugs particularly if taken orally. Clotrimazole is an antifungal medication commonly used in the treatment of fungal infections of both humans and animals such as vaginal yeast infections and ringworm. It also used to treat athlete's foot and jock itch. |
| FRCD ID | F04743 |
| CAS Number | 23593-75-1 |
| PubChem CID | 2812 |
| Formula | C22H17ClN2 |
| IUPAC Name | 1-[(2-chlorophenyl)-diphenylmethyl]imidazole |
| InChI Key | VNFPBHJOKIVQEB-UHFFFAOYSA-N |
| InChI | InChI=1S/C22H17ClN2/c23-21-14-8-7-13-20(21)22(25-16-15-24-17-25,18-9-3-1-4-10-18)19-11-5-2-6-12-19/h1-17H |
| Canonical SMILES | C1=CC=C(C=C1)C(C2=CC=CC=C2)(C3=CC=CC=C3Cl)N4C=CN=C4 |
| Isomeric SMILES | C1=CC=C(C=C1)C(C2=CC=CC=C2)(C3=CC=CC=C3Cl)N4C=CN=C4 |
| Wikipedia | Clotrimazole |
| Synonyms |
Mycosporin
Empecid
Clotrimazol
clotrimazole
23593-75-1
Lotrimin
Canesten
Mycelex
Mykosporin
Gyne lotrimin
|
| Classifies |
Predicted: Pesticide
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Triphenyl compounds |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Triphenyl compounds |
| Alternative Parents | |
| Molecular Framework | Aromatic heteromonocyclic compounds |
| Substituents | Triphenyl compound - Chlorobenzene - Halobenzene - Aryl chloride - Aryl halide - Monocyclic benzene moiety - N-substituted imidazole - Azole - Heteroaromatic compound - Imidazole - Azacycle - Organoheterocyclic compound - Organonitrogen compound - Organic nitrogen compound - Hydrocarbon derivative - Organopnictogen compound - Organochloride - Organohalogen compound - Aromatic heteromonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as triphenyl compounds. These are aromatic compounds containing a triphenyl moiety. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 344.842 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 1 |
| Rotatable Bond Count | 4 |
| Complexity | 396 |
| Monoisotopic Mass | 344.108 |
| Exact Mass | 344.108 |
| XLogP | 5 |
| Formal Charge | 0 |
| Heavy Atom Count | 25 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9837 |
| Human Intestinal Absorption | HIA+ | 0.9725 |
| Caco-2 Permeability | Caco2+ | 0.6858 |
| P-glycoprotein Substrate | Non-substrate | 0.7185 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.6612 |
| Non-inhibitor | 0.7884 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.5854 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.6591 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7898 |
| CYP450 2D6 Substrate | Non-substrate | 0.9149 |
| CYP450 3A4 Substrate | Non-substrate | 0.6262 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.9106 |
| CYP450 2C9 Inhibitor | Inhibitor | 0.8948 |
| CYP450 2D6 Inhibitor | Inhibitor | 0.8932 |
| CYP450 2C19 Inhibitor | Inhibitor | 0.8994 |
| CYP450 3A4 Inhibitor | Inhibitor | 0.8478 |
| CYP Inhibitory Promiscuity | High CYP Inhibitory Promiscuity | 0.9799 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9659 |
| Inhibitor | 0.6779 | |
| AMES Toxicity | Non AMES toxic | 0.7428 |
| Carcinogens | Non-carcinogens | 0.9018 |
| Fish Toxicity | High FHMT | 0.8212 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9713 |
| Honey Bee Toxicity | Low HBT | 0.8379 |
| Biodegradation | Not ready biodegradable | 1.0000 |
| Acute Oral Toxicity | III | 0.7980 |
| Carcinogenicity (Three-class) | Non-required | 0.4730 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -6.0001 | LogS |
| Caco-2 Permeability | 1.5663 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.7194 | LD50, mol/kg |
| Fish Toxicity | 0.0774 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 1.5354 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| A Major Facilitator Superfamily Transporter-Mediated Resistance to OxidativeStress and Fungicides Requires Yap1, Skn7, and MAP Kinases in the Citrus FungalPathogen Alternaria alternata. | PLoS One | 2017 Jan 6 | 28060864 |
| Fusarithioamide A, a new antimicrobial and cytotoxic benzamide derivative fromthe endophytic fungus Fusarium chlamydosporium. | Biochem Biophys Res Commun | 2016 Oct 14 | 27634222 |
| Is it possible to prevent recurrent vulvovaginitis? The role of Lactobacillusplantarum I1001 (CECT7504). | Eur J Clin Microbiol Infect Dis | 2016 Oct | 27393491 |
| Application of hollow fiber membrane mediated with titanium dioxidenanowire/reduced graphene oxide nanocomposite in preconcentration of clotrimazoleand tylosin. | J Chromatogr A | 2015 Nov 13 | 26477522 |
| Effects of food limitation and pharmaceutical compounds on the larval development and morphology of Palaemon serratus. | Sci Total Environ | 2015 Jan 15 | 25240506 |
| Typical azole biocides in biosolid-amended soils and plants following biosolidapplications. | J Agric Food Chem | 2013 Jul 3 | 23756711 |
| QSAR model for human pregnane X receptor (PXR) binding: screening of environmental chemicals and correlations with genotoxicity, endocrine disruption and teratogenicity. | Toxicol Appl Pharmacol | 2012 Aug 1 | 22627063 |
| Susceptibility testing of Aspergillus niger strains isolated from poultry toantifungal drugs--a comparative study of the disk diffusion, broth microdilution (M 38-A) and Etest methods. | Pol J Vet Sci | 2012 | 22708367 |
| Development of a simple liquid chromatography-tandem mass spectrometry method formultiresidue determination of antifungal drugs in chicken tissues. | J AOAC Int | 2011 Sep-Oct | 22165031 |
| Influence of gender, feeding regimen, and exposure duration on gene expression associated with xenobiotic metabolism in fathead minnows (Pimephales promelas). | Comp Biochem Physiol C Toxicol Pharmacol | 2011 Sep | 21664292 |
| Antifungal activity of alpha-mangostin against Candida albicans. | J Oral Sci | 2009 Sep | 19776506 |
| Arachidonic acid increases antifungal susceptibility of Candida albicans andCandida dubliniensis. | J Antimicrob Chemother | 2009 Jan | 18971215 |
| Comparative efficacy of two regimens in syndromic management of lower genitalinfections. | Arch Gynecol Obstet | 2006 Jan | 16247610 |
| Cyclodextrin inclusion complexes of antimycotics intended to act in the oral cavity--drug supersaturation, toxicity on TR146 cells and release from a delivery system. | Eur J Pharm Biopharm | 1999 Nov | 10612032 |
Targets
- General Function:
- Zinc ion binding
- Specific Function:
- Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.
- Gene Name:
- NR1H4
- Uniprot ID:
- Q96RI1
- Molecular Weight:
- 55913.915 Da
References
- Yu DD, Lin W, Chen T, Forman BM: Development of time resolved fluorescence resonance energy transfer-based assay for FXR antagonist discovery. Bioorg Med Chem. 2013 Jul 15;21(14):4266-78. doi: 10.1016/j.bmc.2013.04.069. Epub 2013 May 7. [23688559 ]
- General Function:
- Vitamin d3 25-hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
- Gene Name:
- CYP3A4
- Uniprot ID:
- P08684
- Molecular Weight:
- 57342.67 Da
References
- Roy K, Pratim Roy P: Comparative chemometric modeling of cytochrome 3A4 inhibitory activity of structurally diverse compounds using stepwise MLR, FA-MLR, PLS, GFA, G/PLS and ANN techniques. Eur J Med Chem. 2009 Jul;44(7):2913-22. doi: 10.1016/j.ejmech.2008.12.004. Epub 2008 Dec 16. [19128860 ]
- General Function:
- Interleukin-8 receptor activity
- Specific Function:
- Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activate a phosphatidylinositol-calcium second messenger system. This receptor binds to IL-8 with a high affinity and to MGSA (GRO) with a low affinity.
- Gene Name:
- CXCR1
- Uniprot ID:
- P25024
- Molecular Weight:
- 39790.735 Da
References
- Sassano MF, Doak AK, Roth BL, Shoichet BK: Colloidal aggregation causes inhibition of G protein-coupled receptors. J Med Chem. 2013 Mar 28;56(6):2406-14. doi: 10.1021/jm301749y. Epub 2013 Mar 12. [23437772 ]
- General Function:
- Oxygen binding
- Specific Function:
- Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
- Gene Name:
- CYP19A1
- Uniprot ID:
- P11511
- Molecular Weight:
- 57882.48 Da
References
- Muftuoglu Y, Mustata G: Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg Med Chem Lett. 2010 May 15;20(10):3050-64. doi: 10.1016/j.bmcl.2010.03.113. Epub 2010 Apr 8. [20413308 ]
- General Function:
- Sterol 14-demethylase activity
- Specific Function:
- Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
- Gene Name:
- CYP51A1
- Uniprot ID:
- Q16850
- Molecular Weight:
- 56805.26 Da
References
- Ekins S, Mankowski DC, Hoover DJ, Lawton MP, Treadway JL, Harwood HJ Jr: Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitors. Drug Metab Dispos. 2007 Mar;35(3):493-500. Epub 2006 Dec 28. [17194716 ]
- General Function:
- Voltage-gated ion channel activity
- Specific Function:
- Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.
- Gene Name:
- KCNA3
- Uniprot ID:
- P22001
- Molecular Weight:
- 63841.09 Da
References
- Pegoraro S, Lang M, Dreker T, Kraus J, Hamm S, Meere C, Feurle J, Tasler S, Prutting S, Kuras Z, Visan V, Grissmer S: Inhibitors of potassium channels KV1.3 and IK-1 as immunosuppressants. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2299-304. doi: 10.1016/j.bmcl.2009.02.077. Epub 2009 Feb 25. [19282171 ]
- General Function:
- Steroid 17-alpha-monooxygenase activity
- Specific Function:
- Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty.
- Gene Name:
- CYP17A1
- Uniprot ID:
- P05093
- Molecular Weight:
- 57369.995 Da
References
- Clement OO, Freeman CM, Hartmann RW, Handratta VD, Vasaitis TS, Brodie AM, Njar VC: Three dimensional pharmacophore modeling of human CYP17 inhibitors. Potential agents for prostate cancer therapy. J Med Chem. 2003 Jun 5;46(12):2345-51. [12773039 ]
- General Function:
- Vasopressin receptor activity
- Specific Function:
- Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Involved in renal water reabsorption.
- Gene Name:
- AVPR2
- Uniprot ID:
- P30518
- Molecular Weight:
- 40278.57 Da
References
- Sassano MF, Doak AK, Roth BL, Shoichet BK: Colloidal aggregation causes inhibition of G protein-coupled receptors. J Med Chem. 2013 Mar 28;56(6):2406-14. doi: 10.1021/jm301749y. Epub 2013 Mar 12. [23437772 ]
- Uniprot ID:
- P05184
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
- Gene Name:
- CYP2C9
- Uniprot ID:
- P11712
- Molecular Weight:
- 55627.365 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
- Gene Name:
- CYP2C19
- Uniprot ID:
- P33261
- Molecular Weight:
- 55930.545 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Transcription regulatory region dna binding
- Specific Function:
- Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
- Gene Name:
- AHR
- Uniprot ID:
- P35869
- Molecular Weight:
- 96146.705 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
- Gene Name:
- CYP2D6
- Uniprot ID:
- P10635
- Molecular Weight:
- 55768.94 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Transcriptional activator activity, rna polymerase ii distal enhancer sequence-specific binding
- Specific Function:
- Transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes. Important for the coordinated up-regulation of genes in response to oxidative stress. May be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region.
- Gene Name:
- NFE2L2
- Uniprot ID:
- Q16236
- Molecular Weight:
- 67825.9 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element.
- Gene Name:
- NR1I3
- Uniprot ID:
- Q14994
- Molecular Weight:
- 39942.145 Da
References
- Dau PT, Sakai H, Hirano M, Ishibashi H, Tanaka Y, Kameda K, Fujino T, Kim EY, Iwata H: Quantitative analysis of the interaction of constitutive androstane receptor with chemicals and steroid receptor coactivator 1 using surface plasmon resonance biosensor systems: a case study of the Baikal seal (Pusa sibirica) and the mouse. Toxicol Sci. 2013 Jan;131(1):116-27. doi: 10.1093/toxsci/kfs288. Epub 2012 Sep 26. [23015691 ]
- General Function:
- Xenobiotic-transporting atpase activity
- Specific Function:
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name:
- ABCB1
- Uniprot ID:
- P08183
- Molecular Weight:
- 141477.255 Da
References
- Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [12699389 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
- Gene Name:
- NR1I2
- Uniprot ID:
- O75469
- Molecular Weight:
- 49761.245 Da
References
- Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [20869355 ]
- General Function:
- Protein phosphatase binding
- Specific Function:
- Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:26148990). Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. The channel is blocked by clotrimazole and charybdotoxin but is insensitive to apamin (PubMed:17157250, PubMed:18796614).
- Gene Name:
- KCNN4
- Uniprot ID:
- O15554
- Molecular Weight:
- 47695.12 Da
- Mechanism of Action:
- Clotrimazole interacts with yeast 14-α demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol, an essential component of the membrane. In this way, clotrimazole inhibits ergosterol synthesis, resulting in increased cellular permeability. Clotrimazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms and the uptake of purine, impair triglyceride and/or phospholipid biosynthesis, and inhibit the movement of calcium and potassium ions across the cell membrane by blocking the ion transport pathway known as the Gardos channel.
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- General Function:
- Chemokine receptor activity
- Specific Function:
- High affinity receptor for the C-C type chemokines CCL17/TARC, CCL22/MDC and CKLF isoform 1/CKLF1. The activity of this receptor is mediated by G(i) proteins which activate a phosphatidylinositol-calcium second messenger system. Can function as a chemoattractant homing receptor on circulating memory lymphocytes and as a coreceptor for some primary HIV-2 isolates. In the CNS, could mediate hippocampal-neuron survival.
- Gene Name:
- CCR4
- Uniprot ID:
- P51679
- Molecular Weight:
- 41402.385 Da
References
- Sassano MF, Doak AK, Roth BL, Shoichet BK: Colloidal aggregation causes inhibition of G protein-coupled receptors. J Med Chem. 2013 Mar 28;56(6):2406-14. doi: 10.1021/jm301749y. Epub 2013 Mar 12. [23437772 ]
- General Function:
- Ubiquitin protein ligase binding
- Specific Function:
- Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.
- Gene Name:
- HIF1A
- Uniprot ID:
- Q16665
- Molecular Weight:
- 92669.595 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]