Details of the Drug

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]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 288.4
Logarithm of the Partition Coefficient (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 [3]
Metabolism
The drug is metabolized via the hepatic [4]
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
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

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 [5]
Glucose-6-phosphate dehydrogenase (G6PD) TTKN8W0 G6PD_HUMAN Inhibitor [6]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Multidrug resistance-associated protein 8 (ABCC11) DTWN7FC ABCCB_HUMAN Substrate [7]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [8]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [9]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [10]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [11]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Substrate [12]
Beta-HSD adrenal and gonadal type (HSD3B2) DEN0GVQ 3BHS2_HUMAN Substrate [13]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Substrate [14]
Sulfotransferase 2A1 (SULT2A1) DE0P6LK ST2A1_HUMAN Substrate [15]
Estradiol 17-beta-dehydrogenase 2 (HSD17B2) DEBMFZ8 DHB2_HUMAN Substrate [16]
Estradiol 17-beta-dehydrogenase 1 (HSD17B1) DEZS5YK DHB1_HUMAN Substrate [16]
Dihydrotestosterone oxidoreductase (HSD3B1) DERDQWN 3BHS1_HUMAN Substrate [13]
Peroxisomal multifunctional enzyme 2 (HSD17B4) DEJHG19 DHB4_HUMAN Substrate [16]
Sulfotransferase 2B1 (SULT2B1) DEZBN53 ST2B1_HUMAN Substrate [17]
Cytochrome P450 7B1 (CYP7B1) DE36TMY CP7B1_HUMAN Substrate [18]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) OT6EBDHM DHB1_HUMAN Biotransformations [16]
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) OT3K7HY5 DHB2_HUMAN Biotransformations [16]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Drug Response [19]
Anterior gradient protein 2 homolog (AGR2) OTRRZT7W AGR2_HUMAN Gene/Protein Processing [20]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Gene/Protein Processing [21]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [21]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Protein Interaction/Cellular Processes [22]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Gene/Protein Processing [23]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Biotransformations [24]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Biotransformations [24]
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 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Bioavailability and pharmacokinetics of dehydroepiandrosterone in the cynomolgus monkey
5 Dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, and longevity. Ageing Res Rev. 2004 Apr;3(2):171-87.
6 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.
7 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.
8 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.
9 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
10 Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86.
11 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
12 Urinary and serum octopamine in patients with portal-systemic encephalopathy. Lancet. 1975 Nov 15;2(7942):943-6.
13 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.
14 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
15 Sulfation of environmental estrogens by cytosolic human sulfotransferases. Drug Metab Pharmacokinet. 2002;17(3):221-8.
16 Steroid signalling in the ovarian surface epithelium. Trends Endocrinol Metab. 2005 Sep;16(7):327-33.
17 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.
18 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.
19 TBECH, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane, alters androgen receptor regulation in response to mutations associated with prostate cancer. Toxicol Appl Pharmacol. 2016 Sep 15;307:91-101. doi: 10.1016/j.taap.2016.07.018. Epub 2016 Jul 27.
20 Comparative effects of DHEA and DHT on gene expression in human LNCaP prostate cancer cells. Anticancer Res. 2006 Sep-Oct;26(5A):3205-15.
21 Dehydroepiandrosterone inhibits the proliferation of human umbilical vein endothelial cells by enhancing the expression of p53 and p21, restricting the phosphorylation of retinoblastoma protein, and is androgen- and estrogen-receptor independent. FEBS J. 2005 Mar;272(6):1343-53. doi: 10.1111/j.1742-4658.2005.04563.x.
22 The steroid hormone dehydroepiandrosterone inhibits CYP1A1 expression in vitro by a post-transcriptional mechanism. J Biol Chem. 1999 Dec 3;274(49):35186-90.
23 Dehydroepiandrosterone post-transcriptionally modifies CYP1A2 induction involving androgen receptor. Chem Biol Interact. 2013 May 25;203(3):597-603.
24 Variability of CYP3A7 expression in human fetal liver. J Pharmacol Exp Ther. 2005 Aug;314(2):626-35. doi: 10.1124/jpet.105.086504. Epub 2005 Apr 21.