Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR0929)
Drug Name
Letrozole
Synonyms
Letrozol; Letrozole; Femara; Femera; CGS 20267; CGS-20267; UNII-7LKK855W8I; LETRAZOLE; 112809-51-5; 4,4'-((1h-1,2,4-triazol-1-yl)methylene)dibenzonitrile; 4,4'-(1H-1,2,4-Triazol-1-ylmethylene)dibenzonitrile; 4,4'-(1H-1,2,4-triazol-1-ylmethanediyl)dibenzonitrile; 4,4'-(1h-1,2,4-triazol-1-ylmethylene)bisbenzonitrile; 4-[(4-CYANOPHENYL)(1H-1,2,4-TRIAZOL-1-YL)METHYL]BENZONITRILE; 7LKK855W8I; Benzonitrile, 4,4'-(1H-1,2,4-triazol-1-ylmethylene)bis-; C17H11N5; CHEBI:6413; CHEMBL1444; HSDB 7461
Indication Breast cancer [ICD11: 2C60] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 285.3 Topological Polar Surface Area 78.3
Heavy Atom Count 22 Rotatable Bond Count 3
Hydrogen Bond Donor Count 0 Hydrogen Bond Acceptor Count 4
Cross-matching ID
PubChem CID
3902
PubChem SID
10363 ; 535027 ; 6899006 ; 7848027 ; 7978496 ; 8152457 ; 11112889 ; 11467053 ; 11468173 ; 11486806 ; 12014531 ; 14799856 ; 26719850 ; 29223016 ; 46386665 ; 46504610 ; 46513479 ; 47440364 ; 47736586 ; 47810851 ; 47959864 ; 48416161 ; 49681588 ; 49699256 ; 49830389 ; 49888730 ; 50100535 ; 53789196 ; 56311274 ; 56312145 ; 56313556 ; 56313557 ; 56313754 ; 56352886 ; 57322043 ; 71821268 ; 79643905 ; 81040865 ; 81092820 ; 85787542 ; 92126055 ; 92308318 ; 92308918 ; 92712289 ; 93166173 ; 93167148 ; 99355691 ; 99437044 ; 103513368 ; 103914616
ChEBI ID
ChEBI:6413
CAS Number
112809-51-5
TTD Drug ID
D0C1WH
Formula
C17H11N5
Canonical SMILES
C1=CC(=CC=C1C#N)C(C2=CC=C(C=C2)C#N)N3C=NC=N3
InChI
1S/C17H11N5/c18-9-13-1-5-15(6-2-13)17(22-12-20-11-21-22)16-7-3-14(10-19)4-8-16/h1-8,11-12,17H
InChIKey
HPJKCIUCZWXJDR-UHFFFAOYSA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
Letrozole ketone analog metabolite DM000245 N. A. Unclear 1 [4]
4,4'-methanol-bisbenzonitrile DM000246
10466550
Unclear 2 [4]
Letrozole carbinol glucuronide metabolite DM000247 N. A. Conjugation - Glucuronidation 3 [5]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001447 Letrozole Letrozole ketone analog metabolite Unclear CYP2A6 [4]
MR001445 Letrozole ketone analog metabolite 4,4'-methanol-bisbenzonitrile Unclear CYP3A4 ... [4]
MR001446 4,4'-methanol-bisbenzonitrile Letrozole carbinol glucuronide metabolite Conjugation - Glucuronidation UGT2B7 [5]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Aromatase (CYP19A1) DME0002 Homo sapiens
CP19A_HUMAN
1.14.14.14
[2]
Cytochrome P450 2A6 (CYP2A6) DME0005 Homo sapiens
CP2A6_HUMAN
1.14.14.1
[3]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[4]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DME0040 Homo sapiens
UD2B7_HUMAN
2.4.1.17
[5]
References
1 Letrozole was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients. Eur J Cancer. 1999 Feb;35(2):208-13.
3 Letrozole concentration is associated with CYP2A6 variation but not with arthralgia in patients with breast cancer. Breast Cancer Res Treat. 2018 Nov;172(2):371-379.
4 Inhibition of drug metabolizing cytochrome P450s by the aromatase inhibitor drug letrozole and its major oxidative metabolite 4,4'-methanol-bisbenzonitrile in vitro. Cancer Chemother Pharmacol. 2009 Oct;64(5):867-75.
5 The letrozole phase 1 metabolite carbinol as a novel probe drug for UGT2B7 Drug Metab Dispos. 2013 Nov;41(11):1906-13. doi: 10.1124/dmd.113.053405.

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