Details of the Drug

General Information of Drug (ID: DMVY4GN)

Drug Name
Testolactone
Synonyms
Fludestrin; Teolit; Teslac; Teslak; Testolacton; Testolactona; Testolactonum; Testolattone; Bristol Myers SquibbBrand of Testolactone; Testolattone [DCIT]; SQ 9538; Bristol-Myers Squibb Brand of Testolactone; DELTA1-Dehydrotestolactone; DELTA1-Dehydrotestololactone; DELTA1-Testololactone; SQ-9538; TESLAC (TN);Teslac (TN); Testolactona [INN-Spanish]; Testolactone [USAN:INN]; Testolactonum [INN-Latin]; Delta(1)-Dehydrotestolactone; Delta(1)-Testolactone; Delta(1)-Testololactone; Delta(1)-testololactone; Delta-1-testololactone; Testolactone (USP/INN); D-Homo-17A-oxaandrosta-1,4-diene-3,17-dione; D-homo-17a-oxaandrosta-1,4-diene-3,17-dione; (4aS,4bR,10aR,10bS,12aS)-10a,12a-dimethyl-3,4,4a,5,6,10a,10b,11,12,12a-decahydro-2H-naphtho[2,1-f]chromene-2,8(4bH)-dione; (4aS,4bR,10aR,10bS,12aS)-10a,12a-dimethyl-4,4a,4b,5,6,10b,11,12-octahydro-3H-naphtho[2,1-f]chromene-2,8-dione; 1 Dehydrotestolactone; 1,2,3,4,4a,4b,7,9,10,10a-Decahydro-2-hydroxy-2,4b-dimethyl-7-oxo-1-phenanthrenepropionic acid delta-lactone; 1,2-Dehydrotestololactone; 1,2-Didehydrotestololactone; 1,2-didehydrotestololactone; 1-Dehydrotestolactone; 1-Dehydrotestololactone; 1-dehydrotestololactone; 13,17-Secoandrosta-1,4-dien-17-oic acid, 13-hydroxy-3-oxo-, .delta.-lactone; 13,17-Secoandrosta-1,4-dien-17-oic acid, 13-hydroxy-3-oxo-, delta-lactone; 13,17-Secoandrosta-1,4-dien-17-oic acid, 13-hydroxy-3-oxo-, delta-lactone (8CI); 13,17-Secoandrosta-1,4-dien-17-oic acid, 13-hydroxy-3-oxo-, lactone; 13,17-Secoandrosta-1,4-dien-17-oic acid, 13.alpha.-hydroxy-3-oxo-, .delta.-lactone; 13-Hydroxy-3-oxo-13,17-secoandrosta-1,4-dien-17-oic acid .delta.-lactone; 13-Hydroxy-3-oxo-13,17-secoandrosta-1,4-dien-17-oic acid delta-lactone; 13-hydroxy-3-oxo-13,17-secoandrosta-1,4-dien-17-oic acid delta-lactone; 17a-Oxa-D-homoandrosta-1,4-diene-3,17-dione; 17alpha-Oxo-D-homo-1,4-androstadiene-3,17-dione; 2H-Phenanthro[2,1-b]pyran-2,8(4bH)-dione, 3,4,4a,5,6,10a,10b,11,12,12a-decahydro-10a,12a-dimethyl-, lactone; 3-oxo-13,17-secoandrosta-1,4-dieno-17,13alpha-lactone
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [1], [2]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 300.4
Topological Polar Surface Area (xlogp) 3
Rotatable Bond Count (rotbonds) 0
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Metabolism
The drug is metabolized via the hepatic [4]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 13.88143 micromolar/kg/day [5]
Water Solubility
The ability of drug to dissolve in water is measured as 0.027 mg/mL [3]
Chemical Identifiers
Formula
C19H24O3
IUPAC Name
(4aS,4bR,10aR,10bS,12aS)-10a,12a-dimethyl-4,4a,4b,5,6,10b,11,12-octahydro-3H-naphtho[2,1-f]chromene-2,8-dione
Canonical SMILES
C[C@]12CC[C@H]3[C@H]([C@@H]1CCC(=O)O2)CCC4=CC(=O)C=C[C@]34C
InChI
InChI=1S/C19H24O3/c1-18-9-7-13(20)11-12(18)3-4-14-15(18)8-10-19(2)16(14)5-6-17(21)22-19/h7,9,11,14-16H,3-6,8,10H2,1-2H3/t14-,15+,16+,18+,19+/m1/s1
InChIKey
BPEWUONYVDABNZ-DZBHQSCQSA-N
Cross-matching ID
PubChem CID
13769
ChEBI ID
CHEBI:9460
CAS Number
968-93-4
DrugBank ID
DB00894
TTD ID
D0C7JF

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [6], [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Testolactone (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Carfilzomib DM48K0X Major Additive thrombogenic effects by the combination of Testolactone and Carfilzomib. Multiple myeloma [2A83] [17]
Lonafarnib DMGM2Z6 Moderate Decreased metabolism of Testolactone caused by Lonafarnib mediated inhibition of CYP450 enzyme. Premature ageing appearance [LD2B] [18]

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: 7303).
2 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3 BDDCS applied to over 900 drugs
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 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6 Aromatase inhibitors for male infertility. J Urol. 2002 Feb;167(2 Pt 1):624-9.
7 Testosterone versus testosterone and testolactone in treating reproductive and sexual dysfunction in men with epilepsy and hypogonadism. Neurology. 1998 Mar;50(3):782-4.
8 Effective aromatase inhibition by anastrozole in a patient with gonadotropin-independent precocious puberty in McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2002;15 Suppl 3:945-8.
9 Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51.
10 Aminoglutethimide-induced protein free radical formation on myeloperoxidase: a potential mechanism of agranulocytosis. Chem Res Toxicol. 2007 Jul;20(7):1038-45.
11 Enantioselective nonsteroidal aromatase inhibitors identified through a multidisciplinary medicinal chemistry approach. J Med Chem. 2005 Nov 17;48(23):7282-9.
12 Toremifene-atamestane; alone or in combination: predictions from the preclinical intratumoral aromatase model. J Steroid Biochem Mol Biol. 2008 Jan;108(1-2):1-7.
13 Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg Med Chem Lett. 2010 May 15;20(10):3050-64.
14 Highly potent first examples of dual aromatase-steroid sulfatase inhibitors based on a biphenyl template. J Med Chem. 2010 Mar 11;53(5):2155-70.
15 Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
16 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032111)
17 Cerner Multum, Inc. "Australian Product Information.".
18 Product Information. Zokinvy (lonafarnib). Eiger BioPharmaceuticals, Palo Alto, CA.