General Information of Drug (ID: DM3S8XC)

Drug Name
Dihydrotestosterone
Synonyms
Androstanolone; STANOLONE; dihydrotestosterone; 521-18-6; Andractim; Androlone; Proteina; Anaboleen; Stanaprol; Anabolex; Protona; Neodrol; Cristerona MB; 4-Dihydrotestosterone; 17beta-Hydroxy-5alpha-androstan-3-one; 5alpha-Dihydrotestosterone; Androstanolonum; Androstanolona; DHT; 5-alpha-Dihydrotestosterone; Dihydrotestosteron; Testosterone, dihydro-; 4,5alpha-Dihydrotestosterone; 5alpha-Androstan-17beta-ol-3-one; Stanorone; Stanolon; 17beta-Hydroxyandrostan-3-one; 5alpha-DHT; LG 152; 17beta-Hydroxy-3-androstanone; [3H]dihydrotestosterone
Indication
Disease Entry ICD 11 Status REF
Prostate hyperplasia GA90 Phase 4 [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 290.4
Topological Polar Surface Area (xlogp) 3.7
Rotatable Bond Count (rotbonds) 0
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
Bioavailability
The bioavailability of drug is 0-2% [3]
Chemical Identifiers
Formula
C19H30O2
IUPAC Name
(5S,8R,9S,10S,13S,14S,17S)-17-hydroxy-10,13-dimethyl-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-one
Canonical SMILES
C[C@]12CCC(=O)C[C@@H]1CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC[C@@H]4O)C
InChI
InChI=1S/C19H30O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h12,14-17,21H,3-11H2,1-2H3/t12-,14-,15-,16-,17-,18-,19-/m0/s1
InChIKey
NVKAWKQGWWIWPM-ABEVXSGRSA-N
Cross-matching ID
PubChem CID
10635
ChEBI ID
CHEBI:16330
CAS Number
521-18-6
DrugBank ID
DB02901
TTD ID
D04DJN
VARIDT ID
DR00733
INTEDE ID
DR0114

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Androgen receptor (AR) TTS64P2 ANDR_HUMAN Modulator [4]
Androgen receptor messenger RNA (AR mRNA) TTKPW01 ANDR_HUMAN Agonist [5]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Substrate [7]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Substrate [8]
Aldo-keto reductase 1C1 (AKR1C1) DE7P2FB AK1C1_HUMAN Substrate [9]
Steroid 17-alpha-monooxygenase (CYP17A1) DEX2KIA CP17A_HUMAN Substrate [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Prostate hyperplasia
ICD Disease Classification GA90
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Androgen receptor (AR) DTT AR 2.13E-01 -0.07 -0.11
P-glycoprotein 1 (ABCB1) DTP P-GP 2.80E-02 -1.36E-01 -1.05E+00
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME UGT1A1 6.96E-03 -1.95E-01 -8.72E-01
Steroid 17-alpha-monooxygenase (CYP17A1) DME CYP17A1 2.51E-05 -2.92E-01 -2.29E+00
Aromatase (CYP19A1) DME CYP19A1 1.92E-04 -1.80E-01 -1.31E+00
Aldo-keto reductase 1C1 (AKR1C1) DME AKR1C1 2.85E-02 -3.00E-01 -7.48E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2856).
2 ClinicalTrials.gov (NCT00062790) Effect Of Dutasteride On Intraprostatic Dihydrotestosterone (DHT) Levels. U.S. National Institutes of Health.
3 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4 Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor. Mol Endocrinol. 2002 Jul;16(7):1492-501.
5 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 628).
6 P-glycoprotein increases the efflux of the androgen dihydrotestosterone and reduces androgen responsive gene activity in prostate tumor cells. Prostate. 2004 Apr 1;59(1):77-90.
7 UDP-glucuronosyltransferase 2B15 (UGT2B15) and UGT2B17 enzymes are major determinants of the androgen response in prostate cancer LNCaP cells. J Biol Chem. 2007 Nov 16;282(46):33466-74.
8 Identifying susceptibility genes for prostate cancer--a family-based association study of polymorphisms in CYP17, CYP19, CYP11A1, and LH-beta. Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):2035-9.
9 Human 3-alpha hydroxysteroid dehydrogenase type 3 (3alpha-HSD3): the V54L mutation restricting the steroid alternative binding and enhancing the 20alpha-HSD activity. J Steroid Biochem Mol Biol. 2014 May;141:135-43.
10 Urinary and serum octopamine in patients with portal-systemic encephalopathy. Lancet. 1975 Nov 15;2(7942):943-6.
11 Bidirectional transfer of methadone across human placenta. Biochem Pharmacol. 2005 Jan 1;69(1):187-97.
12 Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients. Eur J Cancer. 1999 Feb;35(2):208-13.
13 Aromatization of testosterone and 19-nortestosterone by a single enzyme from equine testicular microsomes. Differences from human placental aromatase. J Steroid Biochem. 1988 Jan;29(1):119-25.
14 N-demethylation of levo-alpha-acetylmethadol by human placental aromatase. Biochem Pharmacol. 2004 Mar 1;67(5):885-92.
15 Loss of aromatase cytochrome P450 function as a risk factor for Parkinson's disease? Brain Res Rev. 2008 Mar;57(2):431-43.
16 Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
17 Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
18 Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
19 UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
20 Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
21 Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
22 Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
23 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
24 Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
25 Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.
26 Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N-demethylation of aminopyrine. Xenobiotica. 1999 Feb;29(2):187-93.
27 In vitro metabolism of dexamethasone (DEX) in human liver and kidney: the involvement of CYP3A4 and CYP17 (17,20 LYASE) and molecular modelling studies. Biochem Pharmacol. 1997 Sep 1;54(5):605-11.
28 Transcriptional complexes at the CYP17 CRS. Endocr Res. 2002 Nov;28(4):551-8.
29 In vitro metabolism of fenofibric acid by carbonyl reducing enzymes. Chem Biol Interact. 2016 Oct 25;258:153-8.
30 Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes. Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):127-35.
31 The role of carbonyl reducing enzymes in oxcarbazepine in vitro metabolism in man. Chem Biol Interact. 2014 Sep 5;220:241-7.
32 Characterization of enzymes participating in carbonyl reduction of 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in human placenta. Chem Biol Interact. 2001 Jan 30;130-132(1-3):737-48.
33 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
34 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
35 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
36 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
37 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
38 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
39 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
40 Dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, and longevity. Ageing Res Rev. 2004 Apr;3(2):171-87.
41 Androgen receptor as a target in androgen-independent prostate cancer. Urology. 2002 Sep;60(3 Suppl 1):132-8; discussion 138-9.
42 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
43 Molecular mechanism of androgen action. Trends Endocrinol Metab. 1998 Oct 1;9(8):317-24.
44 Ouellet M, Percival MD: Effect of inhibitor time-dependency on selectivity towards cyclooxygenase isoforms. Biochem J. 1995 Feb 15;306 ( Pt 1):247-51.
45 Androgen receptor overexpression induces tamoxifen resistance in human breast cancer cells. Breast Cancer Res Treat. 2010 May;121(1):1-11.
46 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
47 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
48 CX3CR1 is expressed by prostate epithelial cells and androgens regulate the levels of CX3CL1/fractalkine in the bone marrow: potential role in prostate cancer bone tropism. Cancer Res. 2008 Mar 15;68(6):1715-22.
49 Expression of androgen receptor on fibroblast and hepatocyte of rats after deep second-degree burn caused by scalding. Sichuan Da Xue Xue Bao Yi Xue Ban. 2005 May;36(3):362-4.
50 Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist. J Med Chem. 2000 Dec 28;43(26):5010-6.
51 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
52 Clinical pipeline report, company report or official report of ISIS Pharmaceuticals.
53 2011 Pipeline of Santaris Pharma.
54 Effect of essential oils, such as raspberry ketone and its derivatives, on antiandrogenic activity based on in vitro reporter gene assay. Bioorg Med Chem Lett. 2010 Apr 1;20(7):2111-4.
55 Rational design and synthesis of 4-((1R,2R)-2-hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile (PF-998425), a novel, nonsteroidal androgen recepto... J Med Chem. 2008 Nov 13;51(21):7010-4.
56 Effect of flavonoids on androgen and glucocorticoid receptors based on in vitro reporter gene assay. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4706-10.
57 Antiinflammatory glucocorticoid receptor ligand with reduced side effects exhibits an altered protein-protein interaction profile. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19244-9.