General Information of Drug (ID: DMQZ9GF)

Drug Name
Trilostane
Synonyms
Desopan; Desopan (TN); Modrenal (TN); Vetoryl (TN); Vetoryl, Trilostane; Win-24540; Trilostane (JAN/USAN); (4alpha,5alpha,17beta)-3,17-dihydroxy-4,5-epoxyandrost-2-ene-2-carbonitrile; 3,17beta-dihydroxy-4alpha,5-epoxy-5alpha-androst-2-ene-2-carbonitrile
Indication
Disease Entry ICD 11 Status REF
Cushing disease 5A70 Approved [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 329.4
Topological Polar Surface Area (xlogp) 2.9
Rotatable Bond Count (rotbonds) 0
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 4
ADMET Property
Half-life
The concentration or amount of drug in body reduced by one-half in 8 hours [3]
Metabolism
The drug is metabolized via the hepatic [4]
Chemical Identifiers
Formula
C20H27NO3
IUPAC Name
(1S,2R,6R,8S,11S,12S,15S,16S)-5,15-dihydroxy-2,16-dimethyl-7-oxapentacyclo[9.7.0.02,8.06,8.012,16]octadec-4-ene-4-carbonitrile
Canonical SMILES
C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)CC[C@]45[C@@]3(CC(=C([C@H]4O5)O)C#N)C
InChI
InChI=1S/C20H27NO3/c1-18-7-6-14-12(13(18)3-4-15(18)22)5-8-20-17(24-20)16(23)11(10-21)9-19(14,20)2/h12-15,17,22-23H,3-9H2,1-2H3/t12-,13-,14-,15-,17+,18-,19+,20+/m0/s1
InChIKey
KVJXBPDAXMEYOA-CXANFOAXSA-N
Cross-matching ID
PubChem CID
656583
ChEBI ID
CHEBI:32260
CAS Number
13647-35-3
DrugBank ID
DB01108
TTD ID
D03XOC
INTEDE ID
DR1645

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Estrogen receptor beta (ESR2) TTOM3J0 ESR2_HUMAN Modulator [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME
DE4LYSA CP3A4_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Cushing disease
ICD Disease Classification 5A70
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Estrogen receptor beta (ESR2) DTT ESR2 2.09E-01 -0.06 -0.17
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.10E-01 -1.23E-01 -2.88E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

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2 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 018719.
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 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.
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
6 Long-term low-dose ketoconazole treatment in bilateral macronodular adrenal hyperplasia. Endocrinol Diabetes Metab Case Rep. 2014;2014:140083.
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.
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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.
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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 Differential biochemical and cellular actions of Premarin estrogens: distinct pharmacology of bazedoxifene-conjugated estrogens combination. Mol Endocrinol. 2009 Jan;23(1):74-85.
17 Benzothiophene selective estrogen receptor modulators with modulated oxidative activity and receptor affinity. J Med Chem. 2007 May 31;50(11):2682-92.
18 Estrogen inhibits the vascular injury response in estrogen receptor beta-deficient female mice. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15133-6.
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20 MF101, a selective estrogen receptor beta modulator for the treatment of menopausal hot flushes: a phase II clinical trial. Menopause. 2009 May-Jun;16(3):458-65.
21 Company report (Axcentua)
22 S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. Am J Clin Nutr. 2005 May;81(5):1072-9.
23 Erb-041, an estrogen receptor-beta agonist, inhibits skin photocarcinogenesis in SKH-1 hairless mice by downregulating the WNT signaling pathway. Cancer Prev Res (Phila). 2014 Feb;7(2):186-98.
24 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031986)
25 Update on alternative therapies for vulvovaginal atrophy. Patient Prefer Adherence. 2011; 5: 533-536.