General Information of Drug (ID: DM67VKL)

Drug Name
Prasterone
Synonyms
Dehydroepiandrosterone; DHEA; 53-43-0; PRASTERONE; Dehydroisoandrosterone; Androstenolone; trans-Dehydroandrosterone; Psicosterone; Diandrone; Diandron; 3beta-hydroxyandrost-5-en-17-one; 17-Hormoforin; Prestara; 17-Chetovis; Andrestenol; 5-Dehydroepiandrosterone; Intrarosa; Siscelar plus; 5,6-Didehydroisoandrosterone; Dehydro-epi-androsterone; Prasteronum; 5,6-Dehydroisoandrosterone; Prasterona; Epiandrosterone, 5-dehydro-; Caswell No 051F; 5,6-Dehydroisoandrostorone
Indication
Disease Entry ICD 11 Status REF
Chronic obstructive pulmonary disease CA22 Approved [1]
Cardiovascular disease BA00-BE2Z Phase 4 [2], [3]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 288.4
Topological Polar Surface Area (xlogp) 3.2
Rotatable Bond Count (rotbonds) 0
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
Half-life
The concentration or amount of drug in body reduced by one-half in 12 hours [4]
Metabolism
The drug is metabolized via the hepatic [5]
Chemical Identifiers
Formula
C19H28O2
IUPAC Name
(3S,8R,9S,10R,13S,14S)-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one
Canonical SMILES
C[C@]12CC[C@H]3[C@H]([C@@H]1CCC2=O)CC=C4[C@@]3(CC[C@@H](C4)O)C
InChI
InChI=1S/C19H28O2/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/h3,13-16,20H,4-11H2,1-2H3/t13-,14-,15-,16-,18-,19-/m0/s1
InChIKey
FMGSKLZLMKYGDP-USOAJAOKSA-N
Cross-matching ID
PubChem CID
5881
ChEBI ID
CHEBI:28689
CAS Number
53-43-0
DrugBank ID
DB01708
TTD ID
D0K0EK
VARIDT ID
DR01193
INTEDE ID
DR0431

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Androgen receptor (AR) TTS64P2 ANDR_HUMAN Antagonist [6]
Glucose-6-phosphate dehydrogenase (G6PD) TTKN8W0 G6PD_HUMAN Inhibitor [7]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Multidrug resistance-associated protein 8 (ABCC11) DTWN7FC ABCCB_HUMAN Substrate [8]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [9]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [10]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [11]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [12]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Substrate [13]
Beta-HSD adrenal and gonadal type (HSD3B2) DEN0GVQ 3BHS2_HUMAN Substrate [14]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Substrate [15]
Sulfotransferase 2A1 (SULT2A1) DE0P6LK ST2A1_HUMAN Substrate [16]
Estradiol 17-beta-dehydrogenase 2 (HSD17B2) DEBMFZ8 DHB2_HUMAN Substrate [17]
Estradiol 17-beta-dehydrogenase 1 (HSD17B1) DEZS5YK DHB1_HUMAN Substrate [17]
Dihydrotestosterone oxidoreductase (HSD3B1) DERDQWN 3BHS1_HUMAN Substrate [14]
Peroxisomal multifunctional enzyme 2 (HSD17B4) DEJHG19 DHB4_HUMAN Substrate [17]
Sulfotransferase 2B1 (SULT2B1) DEZBN53 ST2B1_HUMAN Substrate [18]
Cytochrome P450 7B1 (CYP7B1) DE36TMY CP7B1_HUMAN Substrate [19]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Chronic obstructive pulmonary disease
ICD Disease Classification CA22
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Androgen receptor (AR) DTT AR 2.13E-01 -0.07 -0.11
Multidrug resistance-associated protein 8 (ABCC11) DTP MRP8 8.53E-01 -1.36E-02 -1.47E-01
Organic anion transporter 3 (SLC22A8) DTP OAT3 4.32E-04 -2.82E-01 -1.59E+00
Breast cancer resistance protein (ABCG2) DTP BCRP 1.91E-02 2.50E-01 1.01E+00
Multidrug resistance-associated protein 4 (ABCC4) DTP MRP4 4.07E-01 2.22E-01 6.78E-01
Estradiol 17-beta-dehydrogenase 1 (HSD17B1) DME HSD17B1 6.19E-01 -3.50E-02 -1.64E-01
Sulfotransferase 2B1 (SULT2B1) DME SULT2B1 6.20E-04 -3.23E-01 -1.55E+00
Dihydrotestosterone oxidoreductase (HSD3B1) DME HSD3B1 5.08E-01 -9.14E-03 -6.31E-02
Aromatase (CYP19A1) DME CYP19A1 1.92E-04 -1.80E-01 -1.31E+00
Beta-HSD adrenal and gonadal type (HSD3B2) DME HSD3B2 5.77E-03 -2.35E-01 -1.08E+00
Peroxisomal multifunctional enzyme 2 (HSD17B4) DME HSD17B4 8.37E-03 -1.16E-01 -7.40E-01
Estradiol 17-beta-dehydrogenase 2 (HSD17B2) DME HSD17B2 1.04E-04 -2.41E-01 -1.69E+00
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 7.93E-02 -8.20E-02 -8.93E-01
Cytochrome P450 7B1 (CYP7B1) DME CYP7B1 7.78E-02 6.64E-02 8.61E-01
Sulfotransferase 2A1 (SULT2A1) DME SULT2A1 6.05E-02 -4.22E-02 -5.22E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Direct agonist/antagonist functions of dehydroepiandrosterone. Endocrinology. 2005 Nov;146(11):4568-76.
2 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: 2370).
3 ClinicalTrials.gov (NCT02357472) The Effect of a Higher Dose of Dehydroepiandrosterone (DHEA) Supplementation in Poor Responders. U.S. National Institutes of Health.
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Bioavailability and pharmacokinetics of dehydroepiandrosterone in the cynomolgus monkey
6 Dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, and longevity. Ageing Res Rev. 2004 Apr;3(2):171-87.
7 Glucose utilization and activity of glucose-6-phosphate dehydrogenase, isocitrate dehydrogenase and malate dehydrogenase in rat erythrocytes after treatment with tuberculostatic agents. Vopr Med Khim. 1986 Sep-Oct;32(5):32-5.
8 Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system. Neuroscience. 2006;137(4):1247-57.
9 Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem J. 2003 Apr 15;371(Pt 2):361-7.
10 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
11 Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86.
12 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
13 Urinary and serum octopamine in patients with portal-systemic encephalopathy. Lancet. 1975 Nov 15;2(7942):943-6.
14 Selective inhibition of human 3beta-hydroxysteroid dehydrogenase type 1 as a potential treatment for breast cancer. J Steroid Biochem Mol Biol. 2011 May;125(1-2):57-65.
15 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
16 Sulfation of environmental estrogens by cytosolic human sulfotransferases. Drug Metab Pharmacokinet. 2002;17(3):221-8.
17 Steroid signalling in the ovarian surface epithelium. Trends Endocrinol Metab. 2005 Sep;16(7):327-33.
18 Expression and characterization of the human 3 beta-hydroxysteroid sulfotransferases (SULT2B1a and SULT2B1b). J Steroid Biochem Mol Biol. 2001 Jun;77(4-5):261-9.
19 CYP7B1-mediated metabolism of dehydroepiandrosterone and 5alpha-androstane-3beta,17beta-diol--potential role(s) for estrogen signaling. FEBS J. 2008 Apr;275(8):1778-89.
20 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
21 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
22 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
23 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
24 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
25 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
26 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
27 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
28 Cytochrome P450 3A4-mediated interaction of diclofenac and quinidine. Drug Metab Dispos. 2000 Sep;28(9):1043-50.
29 Bidirectional transfer of methadone across human placenta. Biochem Pharmacol. 2005 Jan 1;69(1):187-97.
30 Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients. Eur J Cancer. 1999 Feb;35(2):208-13.
31 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.
32 N-demethylation of levo-alpha-acetylmethadol by human placental aromatase. Biochem Pharmacol. 2004 Mar 1;67(5):885-92.
33 Loss of aromatase cytochrome P450 function as a risk factor for Parkinson's disease? Brain Res Rev. 2008 Mar;57(2):431-43.
34 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.
35 The role of cytochrome P450 3A (CYP3A) isoform(s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver. J Steroid Biochem Mol Biol. 1993 Jan;44(1):61-7.
36 Drug Interactions Flockhart Table
37 Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos. 2004 Feb;32(2):259-66.
38 The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.
39 Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers.
40 Abiraterone for the treatment of metastatic castrate-resistant prostate cancer. Ann Pharmacother. 2012 Jul-Aug;46(7-8):1016-24.
41 In vitro metabolism of TAK-438, vonoprazan fumarate, a novel potassium-competitive acid blocker. Xenobiotica. 2017 Dec;47(12):1027-1034.
42 Human mass balance, metabolite profile and identification of metabolic enzymes of [14C]ASP015K, a novel oral janus kinase inhibitor. Xenobiotica. 2015;45(10):887-902.
43 Interindividual variability in acetaminophen sulfation by human fetal liver: implications for pharmacogenetic investigations of drug-induced birth defects. Birth Defects Res A Clin Mol Teratol. 2008 Mar;82(3):155-65.
44 Tibolone: a unique version of hormone replacement therapy. Ann Pharmacother. 2004 May;38(5):874-81.
45 Structure/function relationships responsible for the kinetic differences between human type 1 and type 2 3beta-hydroxysteroid dehydrogenase and for the catalysis of the type 1 activity. J Biol Chem. 2002 Nov 8;277(45):42795-801.
46 Hormonal properties of norethisterone, 7alpha-methyl-norethisterone and their derivatives. J Steroid Biochem Mol Biol. 2000 Nov 15;74(4):213-22.
47 Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
48 Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
49 The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
50 Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
51 Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
52 Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
53 The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
54 Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
55 Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
56 Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport. J Pharmacol Exp Ther. 2007 Jan;320(1):229-35.
57 Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50.
58 ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells. Pancreatology. 2009;9(1-2):136-44.
59 The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9.
60 P-glycoprotein, but not multidrug resistance protein 4, plays a role in the systemic clearance of irinotecan and SN-38 in mice. Drug Metab Lett. 2010 Dec;4(4):195-201.
61 Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia. Blood. 2009 Aug 13;114(7):1383-6.
62 Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues. Biochem J. 2002 Feb 1;361(Pt 3):497-503.
63 Oral availability of cefadroxil depends on ABCC3 and ABCC4. Drug Metab Dispos. 2012 Mar;40(3):515-21.
64 Methotrexate-loxoprofen interaction: involvement of human organic anion transporters hOAT1 and hOAT3. Drug Metab Pharmacokinet. 2004 Oct;19(5):369-74.
65 Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
66 Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
67 Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments. Drug Metab Dispos. 2011 Jun;39(6):1031-8.
68 Murine renal organic anion transporters mOAT1 and mOAT3 facilitate the transport of neuroactive tryptophan metabolites. Am J Physiol Cell Physiol. 2005 Nov;289(5):C1075-84.
69 Organic anion transporter 3 is involved in the brain-to-blood efflux transport of thiopurine nucleobase analogs. J Neurochem. 2004 Aug;90(4):931-41.
70 Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
71 The contribution of organic anion transporters OAT1 and OAT3 to the renal uptake of rosuvastatin. J Pharmacol Exp Ther. 2007 Sep;322(3):1221-7.
72 Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat. Drug Metab Dispos. 2014 Jun;42(6):996-1007.
73 Expression of organic anion transporter 2 in the human kidney and its potential role in the tubular secretion of guanine-containing antiviral drugs. Drug Metab Dispos. 2012 Mar;40(3):617-24.
74 ABCC11/MRP8 confers pemetrexed resistance in lung cancer. Cancer Sci. 2010 Nov;101(11):2404-10.
75 MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2',3'-dideoxycytidine and 9'-(2'-phosphonylmethoxyethyl)adenine. J Biol Chem. 2003 Aug 8;278(32):29509-14.
76 Tenofovir Disoproxil Fumarate Is a New Substrate of ATP-Binding Cassette Subfamily C Member 11. Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e01725-16.
77 Androgen receptor as a target in androgen-independent prostate cancer. Urology. 2002 Sep;60(3 Suppl 1):132-8; discussion 138-9.
78 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
79 Molecular mechanism of androgen action. Trends Endocrinol Metab. 1998 Oct 1;9(8):317-24.
80 Ouellet M, Percival MD: Effect of inhibitor time-dependency on selectivity towards cyclooxygenase isoforms. Biochem J. 1995 Feb 15;306 ( Pt 1):247-51.
81 Androgen receptor overexpression induces tamoxifen resistance in human breast cancer cells. Breast Cancer Res Treat. 2010 May;121(1):1-11.
82 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
83 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
84 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.
85 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.
86 An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology. 2007 Jan;148(1):363-73.
87 Inhibition of Trypanosoma brucei glucose-6-phosphate dehydrogenase by human steroids and their effects on the viability of cultured parasites. Bioorg Med Chem. 2009 Mar 15;17(6):2483-9.
88 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007279)
89 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.