Details of the Drug

General Information of Drug (ID: DMPMDTH)

Drug Name
Azd9496
Synonyms
DFBDRVGWBHBJNR-BBNFHIFMSA-N; 1639042-08-2; UNII-DA9P7LN909; DA9P7LN909; CHEMBL3623004; AZD-9496; (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid; (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido(3,4-b)indol-1-yl)phenyl)acrylic acid; SCHEMBL16266273; SCHEMBL16266275; MolPort-044-560-384; EX-A1326; s8372; BDBM50125052; ZINC219669733; AKOS030526632; AC-29011; HY-12870; Selective estrogen
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 1 [1]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 442.5
Topological Polar Surface Area (xlogp) 2.9
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C25H25F3N2O2
IUPAC Name
(E)-3-[3,5-difluoro-4-[(1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]prop-2-enoic acid
Canonical SMILES
C[C@@H]1CC2=C([C@H](N1CC(C)(C)F)C3=C(C=C(C=C3F)/C=C/C(=O)O)F)NC4=CC=CC=C24
InChI
InChI=1S/C25H25F3N2O2/c1-14-10-17-16-6-4-5-7-20(16)29-23(17)24(30(14)13-25(2,3)28)22-18(26)11-15(12-19(22)27)8-9-21(31)32/h4-9,11-12,14,24,29H,10,13H2,1-3H3,(H,31,32)/b9-8+/t14-,24-/m1/s1
InChIKey
DFBDRVGWBHBJNR-BBNFHIFMSA-N
Cross-matching ID
PubChem CID
86287635
CAS Number
1639042-08-2
TTD ID
D0X1OW
INTEDE ID
DR1801

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Estrogen receptor (ESR) TTZAYWL ESR1_HUMAN Antagonist [1]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2C8 (CYP2C8)
Main DME 		DES5XRU CP2C8_HUMAN Substrate [2]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Breast cancer
ICD Disease Classification 2C60-2C65
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Cytochrome P450 2C8 (CYP2C8) DME CYP2C8 9.78E-01 -3.38E-03 -5.71E-02
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2 Complete substrate inhibition of cytochrome P450 2C8 by AZD9496, an oral selective estrogen receptor degrader. Drug Metab Dispos. 2018 Sep;46(9):1268-1276.
3 Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
4 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
5 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
6 Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
7 Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
8 Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
9 PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
10 Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
11 Modulators of vascular sex hormone receptors and their effects in estrogen-deficiency states associated with menopause. Recent Pat Cardiovasc Drug Discov. 2008 Nov;3(3):165-86.
12 Reprint of Are all estrogens the same Maturitas. 2008 Sep-Oct;61(1-2):195-201.
13 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
14 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8.
15 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: 620).
16 Clinical pipeline report, company report or official report of Shionogi (2011).
17 Effect of selective estrogen receptor modulators on cell proliferation and estrogen receptor activities in normal human prostate stromal and epithe... Prostate Cancer Prostatic Dis. 2009;12(4):375-81.