Clotrimazole (T3D2729)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (22)XML
Targets (22)
Record Information
Version2.0
Creation Date2009-07-21 20:26:25 UTC
Update Date2014-12-24 20:25:50 UTC
Accession NumberT3D2729
Identification
Common NameClotrimazole
ClassSmall Molecule
DescriptionClotrimazole 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.
Compound Type
  • 14-alpha Demethylase Inhibitor
  • Amine
  • Anti-Infective Agent, Local
  • Antifungal Agent
  • Drug
  • Food Toxin
  • Growth Inhibitor
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
(Chlorotrityl)imidazole
1-((2-Chlorophenyl)diphenylmethyl)-1H-imidazole
1-(alpha-(2-Chlorophenyl)benzhydryl)imidazole
1-(O-Chloro-alpha,alpha-diphenylbenzyl)imidazole
1-(o-Chloro-α,α-diphenylbenzyl)imidazole
1-(O-Chlorotrityl)imidazole
1-(α-(2-Chlorophenyl)benzhydryl)imidazole
Canesten
Canesten 1-Day Cream Combi-Pak
Canesten 1-Day Therapy
Canesten 3-Day Therapy
Canesten 6-Day Therapy
Canesten Combi-Pak 1-Day Therapy
Canesten Combi-Pak 3-Day Therapy
Canesten Cream
Canesten Solution
Canestine
Canifug
Chlotrimazole
Clotrimaderm
Clotrimaderm Cream
Clotrimazol
Clotrimazolum
Desamix F
Empecid
Fem Care
FemCare
Fungicip
Gyne lotrimin
Gyne-lotrimin
Gyne-Lotrimin 3
Gyne-Lotrimin 3 Combination Pack
Gyne-Lotrimin Combination Pack
Gyne-Lotrimin3
Gyne-Lotrimin3 Combination Pack
Gynix
Lopac-C-6019
Lotrimax
Lotrimin
Lotrimin AF
Lotrimin AF Cream
Lotrimin AF Jock-Itch Cream
Lotrimin AF Lotion
Lotrimin AF Solution
Lotrimin Cream
Lotrimin Lotion
Lotrimin Solution
Lotrisone
Mono-baycuten
Monobaycuten
Mycelax
Mycelex
Mycelex 7
Mycelex Cream
Mycelex G
Mycelex OTC
Mycelex Solution
Mycelex Troches
Mycelex Twin Pack
Mycelex-7
Mycelex-7 Combination Pack
Mycelex-G
Mycelex: MycosporinRimazole
Myclo Cream
Myclo Solution
Myclo Spray Solution
Myclo-Derm
Myclo-Gyne
Mycosporin
Mykosporin
Neo-Zol Cream
Otomax
Pedisafe
Prestwick_120
Rimazole
Tibatin
Trimysten
Trivagizole 3
Veltrim
Chemical FormulaC22H17ClN2
Average Molecular Mass344.837 g/mol
Monoisotopic Mass344.108 g/mol
CAS Registry Number23593-75-1
IUPAC Name1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole
Traditional Nameclotrimazole
SMILESClC1=CC=CC=C1C(N1C=CN=C1)(C1=CC=CC=C1)C1=CC=CC=C1
InChI IdentifierInChI=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
InChI KeyInChIKey=VNFPBHJOKIVQEB-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as triphenyl compounds. These are aromatic compounds containing a triphenyl moiety.
KingdomOrganic compounds
Super ClassBenzenoids
ClassTriphenyl compounds
Sub ClassNot Available
Direct ParentTriphenyl compounds
Alternative Parents
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
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Skin
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point154-156°C
Boiling PointNot Available
Solubility29.84 mg/mL
LogP6.1
Predicted Properties
PropertyValueSource
Water Solubility0.0015 g/LALOGPS
logP5.48ALOGPS
logP5.84ChemAxon
logS-5.4ALOGPS
pKa (Strongest Basic)6.62ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area17.82 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity103.76 m³·mol⁻¹ChemAxon
Polarizability36.25 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0059-6090000000-3cccc4c11a7c5a63573d2017-08-28View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, N/A (Annotated)splash10-004i-0090000000-9ac001e37a55e61bc9162012-07-25View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, N/A (Annotated)splash10-004i-0290000000-6285150b307e50af52c72012-07-25View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, N/A (Annotated)splash10-016u-0690000000-5814802384fae84ca3df2012-07-25View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0090000000-23b69c41217f6b1483072017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-016r-0960000000-5b3632c056ca1c0fa6012017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-016r-0950000000-bcb189995c8cdcd623042017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0090000000-f1d5f44ac74388f9bf4f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-004i-1490000000-1ed188e9911ad62a7fc72017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-004i-0390000000-c2f0490842646cf25d562017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-014l-3970000000-0cf80068015e539b67c92017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00or-0391000000-e8d9d4c77703a87fdcd82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-004i-0090000000-0df2bee4ed15192bc0b62021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-004i-0090000000-f0198e4e7eaad2f341472021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-00or-0490000000-53d8902c6f7211fc3c502021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-014i-0950000000-168bf9867190bc3708b32021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-014i-0950000000-c0c372245eb2fe021e2e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-004i-0090000000-23b69c41217f6b1483072021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-004i-0090000000-f1d5f44ac74388f9bf4f2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-016r-0960000000-5b3632c056ca1c0fa6012021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0019000000-a5e5b5c85ea879e2f63b2017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00kb-1039000000-cf9a51f1cb5d717c41692017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-9280000000-7b57b00ebea4c6a2f8642017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0009000000-416f1aa58c794269d0382017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-1009000000-25f48116b270c282f4772017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014i-8192000000-fb089a74161c7e17e5da2017-07-26View Spectrum
MSMass Spectrum (Electron Ionization)splash10-004i-1490000000-442fa75d6a2d80321e362014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, CD3OD, experimental)Not Available2012-12-05View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, CD3OD, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposurePoorly and erratically absorbed orally, minimal vaginal or topical absorption.
Mechanism of ToxicityClotrimazole 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.
MetabolismHepatic (metabolized to inactive metabolites) Half Life: 2 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the local treatment of oropharyngeal candidiasis and vaginal yeast infections, also used in fungal infections of the skin such as ringworm, athlete's foot, and jock itch.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin, and cramps.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00257
HMDB IDHMDB01922
PubChem Compound ID2812
ChEMBL IDCHEMBL104
ChemSpider ID2710
KEGG IDC06922
UniProt IDNot Available
OMIM ID
ChEBI ID3764
BioCyc IDNot Available
CTD IDNot Available
Stitch IDClotrimazole
PDB IDCL6
ACToR IDNot Available
Wikipedia LinkClotrimazole
References
Synthesis Reference

Buechel, K.H., et al; South African Patent 69/0039; January 3, 1969; assigned to Farben- Buechel, K.H., Regel, E. and Plempel, M.; US. Patent 3,660,577; May 2,1972; and U.S. fabriken Bayer AG, Germany.
Patent 3,705,172; Dec. 5,1972; both assigned to Farbenfabriken Bayer A.G. (Germany).

MSDSLink
General References
  1. Lucker PW, Beubler E, Kukovetz WR, Ritter W: Retention time and concentration in human skin of bifonazole and clotrimazole. Dermatologica. 1984;169 Suppl 1:51-5. [6526092 ]
  2. Schmidt A, Ruhl-Horster B: In vitro susceptibility of Malassezia furfur against azole compounds. Mycoses. 1996 Jul-Aug;39(7-8):309-12. [9009652 ]
  3. Schmook FP, Meingassner JG, Billich A: Comparison of human skin or epidermis models with human and animal skin in in-vitro percutaneous absorption. Int J Pharm. 2001 Mar 14;215(1-2):51-6. [11250091 ]
  4. Drugs.com [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

Target Details
1. Nuclear receptor subfamily 1 group I member 2
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.46 uMATG_PXR_TRANSAttagene
AC500.85 uMATG_PXRE_CISAttagene
References
  1. Faucette SR, Wang H, Hamilton GA, Jolley SL, Gilbert D, Lindley C, Yan B, Negishi M, LeCluyse EL: Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. Drug Metab Dispos. 2004 Mar;32(3):348-58. [14977870 ]
  2. Smith CM, Faucette SR, Wang H, LeCluyse EL: Modulation of UDP-glucuronosyltransferase 1A1 in primary human hepatocytes by prototypical inducers. J Biochem Mol Toxicol. 2005;19(2):96-108. [15849716 ]
  3. 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 ]
  4. 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 ]
Target Details
2. Bile acid receptor
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC503.24 uMNot AvailableBindingDB 31774
AC504.41 uMOT_SRC1_SRC1FXR_1440Odyssey Thera
References
  1. 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 ]
  2. 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 ]
Target Details
3. Intermediate conductance calcium-activated potassium channel protein 4
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.07 uMNot AvailableBindingDB 31774
IC500.36 uMNot AvailableBindingDB 31774
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. 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 ]
  3. McNaughton-Smith GA, Burns JF, Stocker JW, Rigdon GC, Creech C, Arrington S, Shelton T, de Franceschi L: Novel inhibitors of the Gardos channel for the treatment of sickle cell disease. J Med Chem. 2008 Feb 28;51(4):976-82. doi: 10.1021/jm070663s. Epub 2008 Jan 31. [18232633 ]
Target Details
4. Cytochrome P450 3A4
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.02 uMNot AvailableBindingDB 31774
IC500.05 uMNot AvailableBindingDB 31774
References
  1. 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 ]
  2. 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 ]
Target Details
5. Multidrug resistance protein 1
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501.3 uMNot AvailableBindingDB 31774
IC506.7 uMNot AvailableBindingDB 31774
References
  1. 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 ]
  2. Bain LJ, LeBlanc GA: Interaction of structurally diverse pesticides with the human MDR1 gene product P-glycoprotein. Toxicol Appl Pharmacol. 1996 Nov;141(1):288-98. [8917702 ]
Target Details
6. C-C chemokine receptor type 4
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501.6 uMNot AvailableBindingDB 31774
References
  1. 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 ]
Target Details
7. C-X-C chemokine receptor type 1
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC502 uMNot AvailableBindingDB 31774
IC507.9 uMNot AvailableBindingDB 31774
IC5010.8 uMNot AvailableBindingDB 31774
References
  1. 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 ]
Target Details
8. Aromatase
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.0018 uMNot AvailableBindingDB 31774
References
  1. 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 ]
Target Details
9. Lanosterol 14-alpha demethylase
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.13 uMNot AvailableBindingDB 31774
References
  1. 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 ]
Target Details
10. Malate dehydrogenase, cytoplasmic
General Function:
Nad binding
Specific Function:
Not Available
Gene Name:
MDH1
Uniprot ID:
P40925
Molecular Weight:
36425.795 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5035 uMNot AvailableBindingDB 31774
References
  1. Seidler J, McGovern SL, Doman TN, Shoichet BK: Identification and prediction of promiscuous aggregating inhibitors among known drugs. J Med Chem. 2003 Oct 9;46(21):4477-86. [14521410 ]
Target Details
11. Nuclear receptor subfamily 1 group I member 3
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
  1. 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 ]
Target Details
12. Potassium voltage-gated channel subfamily A member 3
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC506 uMNot AvailableBindingDB 31774
References
  1. 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 ]
Target Details
13. Steroid 17-alpha-hydroxylase/17,20 lyase
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0815 uMNot AvailableBindingDB 31774
References
  1. 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 ]
Target Details
14. Vasopressin V2 receptor
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC502.7 uMNot AvailableBindingDB 31774
IC5015.1 uMNot AvailableBindingDB 31774
References
  1. 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 ]
Target Details
15. Cytochrome P450 3A4
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.04 uMNVS_ADME_hCYP3A4Novascreen
References
  1. 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 ]
Target Details
16. Hypoxia-inducible factor 1-alpha
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.04 uMATG_HIF1a_CISAttagene
References
  1. 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 ]
Target Details
17. Cytochrome P450 2C9
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.60 uMNVS_ADME_hCYP2C9Novascreen
References
  1. 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 ]
Target Details
18. Estrogen receptor
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.93 uMATG_ERa_TRANSAttagene
References
  1. 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 ]
Target Details
19. Cytochrome P450 2C19
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.10 uMNVS_ADME_hCYP2C19Novascreen
References
  1. 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 ]
Target Details
20. Aryl hydrocarbon receptor
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.60 uMATG_Ahr_CISAttagene
AC502.33 uMTox21_AhRTox21/NCGC
References
  1. 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 ]
Target Details
21. Cytochrome P450 2D6
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.53 uMNVS_ADME_hCYP2D6Novascreen
References
  1. 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 ]
Target Details
22. Nuclear factor erythroid 2-related factor 2
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.07 uMATG_NRF2_ARE_CISAttagene
References
  1. 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 ]