General Information of Drug (ID: DM6VFO1)

Drug Name
Pregnenolone
Synonyms Pregnenolone (schizophrenia); Neurosteroid (schizophrenia), Neuroscience; Pregnenolone (schizophrenia), Neuroscience
Indication
Disease Entry ICD 11 Status REF
Schizophrenia 6A20 Phase 4 [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 316.5
Topological Polar Surface Area (xlogp) 4.2
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 2
Chemical Identifiers
Formula
C21H32O2
IUPAC Name
1-[(3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone
Canonical SMILES
CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H](C4)O)C)C
InChI
InChI=1S/C21H32O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h4,15-19,23H,5-12H2,1-3H3/t15-,16-,17+,18-,19-,20-,21+/m0/s1
InChIKey
ORNBQBCIOKFOEO-QGVNFLHTSA-N
Cross-matching ID
PubChem CID
8955
ChEBI ID
CHEBI:16581
CAS Number
145-13-1
DrugBank ID
DB02789
TTD ID
D0B4RU
INTEDE ID
DR1336

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Estrogen-related receptor-alpha (ESRRA) TTPNQAC ERR1_HUMAN Agonist [3]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [4]
Beta-HSD adrenal and gonadal type (HSD3B2) DEN0GVQ 3BHS2_HUMAN Substrate [5]
Sulfotransferase 2A1 (SULT2A1) DE0P6LK ST2A1_HUMAN Substrate [6]
Dihydrotestosterone oxidoreductase (HSD3B1) DERDQWN 3BHS1_HUMAN Substrate [5]
Sulfotransferase 2B1 (SULT2B1) DEZBN53 ST2B1_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

ICD Disease Classification 06 Mental, behavioural or neurodevelopmental disorder
Disease Class ICD-11: 6A20 Schizophrenia
The Studied Tissue Pre-frontal cortex
The Studied Disease Schizophrenia [ICD-11:6A20]
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Estrogen-related receptor-alpha (ESRRA) DTT ESRRA 9.34E-01 1.47E-02 0.06
Estrogen-related receptor-alpha (ESRRA) DTT ESRRA 2.09E-01 -0.07 -0.62
Sulfotransferase 2B1 (SULT2B1) DME SULT2B1 9.69E-01 3.48E-03 1.02E-02
Sulfotransferase 2B1 (SULT2B1) DME SULT2B1 8.40E-01 6.15E-02 3.66E-01
Dihydrotestosterone oxidoreductase (HSD3B1) DME HSD3B1 2.84E-01 -8.57E-03 -6.45E-02
Dihydrotestosterone oxidoreductase (HSD3B1) DME HSD3B1 7.78E-01 4.16E-03 5.82E-02
Beta-HSD adrenal and gonadal type (HSD3B2) DME HSD3B2 2.39E-01 5.15E-02 2.14E-01
Beta-HSD adrenal and gonadal type (HSD3B2) DME HSD3B2 8.14E-01 -2.28E-02 -1.48E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 4.66E-01 4.25E-02 1.20E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 4.75E-01 5.15E-02 3.64E-01
Sulfotransferase 2A1 (SULT2A1) DME SULT2A1 7.80E-01 -1.17E-03 -9.90E-03
Sulfotransferase 2A1 (SULT2A1) DME SULT2A1 1.01E-01 -1.06E-02 -1.31E-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: 2376).
2 ClinicalTrials.gov (NCT01409096) Study Using Pregnenolone to Treat Bipolar Depression. U.S. National Institutes of Health.
3 Suppression of adrenal function by low-dose prednisone: assessment with 24-hour urinary steroid hormone profiles--a review of five cases. Altern Med Rev. 2006 Mar;11(1):40-6.
4 Cytochrome P450 expression and regulation in CYP3A4/CYP2D6 double transgenic humanized mice. Drug Metab Dispos. 2008 Feb;36(2):435-41.
5 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.
6 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.
7 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.
8 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
9 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.
10 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
11 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.
12 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.
13 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
14 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.
15 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.
16 Sulfation of environmental estrogens by cytosolic human sulfotransferases. Drug Metab Pharmacokinet. 2002;17(3):221-8.
17 Abiraterone for the treatment of metastatic castrate-resistant prostate cancer. Ann Pharmacother. 2012 Jul-Aug;46(7-8):1016-24.
18 In vitro metabolism of TAK-438, vonoprazan fumarate, a novel potassium-competitive acid blocker. Xenobiotica. 2017 Dec;47(12):1027-1034.
19 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.
20 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.
21 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.
22 Tibolone: a unique version of hormone replacement therapy. Ann Pharmacother. 2004 May;38(5):874-81.
23 Steroid signalling in the ovarian surface epithelium. Trends Endocrinol Metab. 2005 Sep;16(7):327-33.
24 Hormonal properties of norethisterone, 7alpha-methyl-norethisterone and their derivatives. J Steroid Biochem Mol Biol. 2000 Nov 15;74(4):213-22.
25 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: 622).
26 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007199)
27 Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial. Lancet. 2002 Jul 20;360(9328):211-8.
28 Use of the steroid derivative RPR 106541 in combination with site-directed mutagenesis for enhanced cytochrome P-450 3A4 structure/function analysis. J Pharmacol Exp Ther. 1999 Aug;290(2):594-602.
29 Direct activation of GABAA receptors by loreclezole, an anticonvulsant drug with selectivity for the beta-subunit. Neuropharmacology. 1996;35(12):1753-60.
30 The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin Endocrinol (Oxf). 1998 Oct;49(4):421-32.
31 Flavone and isoflavone phytoestrogens are agonists of estrogen-related receptors. Mol Cancer Res. 2003 Nov;1(13):981-91.