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

General Information of Drug (ID: DR0560)
Drug Name
Efavirenz
Synonyms
Stocrin; Sustiva; Efavirenz; DMP 266; DMP-266; L-743,726; L-743726; (-)-6-CHLORO-4-CYCLOPROPYLETHYNYL-4-TRIFLUOROMETHYL-1,4-DIHYDRO-2H-3,1-BENZOXAZIN-2-ONE; (4S)-6-Chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one; (4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1H-3,1-benzoxazin-2-one; (S)-6-Chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one; 154598-52-4; EFV; HSDB 7163; UNII-JE6H2O27P8
Indication Human immunodeficiency virus infection [ICD11: 1C60] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 315.67 Topological Polar Surface Area 38.3
Heavy Atom Count 21 Rotatable Bond Count 1
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 5
Cross-matching ID
PubChem CID
64139
PubChem SID
10288 ; 615076 ; 644086 ; 819805 ; 819816 ; 822777 ; 822778 ; 823557 ; 2102933 ; 7847960 ; 7887287 ; 7979148 ; 8032270 ; 8189153 ; 12014858 ; 14850291 ; 26719858 ; 43121048 ; 46386724 ; 46392227 ; 46392228 ; 46506827 ; 49681705 ; 50064506 ; 53788925 ; 57315036 ; 78192089 ; 87350529 ; 91146581 ; 92308418 ; 92309272 ; 92717165 ; 93166541 ; 99444180 ; 104234240 ; 104330198 ; 118313744 ; 124658998 ; 126592964 ; 126608811 ; 126622440 ; 126654055 ; 129722732 ; 131300250 ; 134337998 ; 135022248 ; 136367956 ; 136903808 ; 137005170 ; 137229934
ChEBI ID
CHEBI:119486
CAS Number
154598-52-4
TTD Drug ID
D07HVY
Formula
C14H9ClF3NO2
Canonical SMILES
C1CC1C#CC2(C3=C(C=CC(=C3)Cl)NC(=O)O2)C(F)(F)F
InChI
1S/C14H9ClF3NO2/c15-9-3-4-11-10(7-9)13(14(16,17)18,21-12(20)19-11)6-5-8-1-2-8/h3-4,7-8H,1-2H2,(H,19,20)/t13-/m0/s1
InChIKey
XPOQHMRABVBWPR-ZDUSSCGKSA-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
8-hydroxy-efavirenz DM000564
487643
Oxidation - Hydroxylation 1 [5] , [3] , [6] , [7]
Efavirenz metabolite M2 DM000571 N. A. Conjugation - Conjugation 1 [8]
Efavirenz metabolite M5 DM000568 N. A. Oxidation - Hydroxylation 1 [8]
Efavirenz metabolite M1 DM000567 N. A. Conjugation - Conjugation 2 [8] , [9]
Efavirenz metabolite M6 DM000569 N. A. Conjugation - Conjugation 2 [8]
Efavirenz metabolite M7 DM000570 N. A. Conjugation - Conjugation 2 [8]
Efavirenz metabolite M8 DM000565
16725849
Oxidation - Hydroxylation 2 [5] , [10] , [4]
Efavirenz metabolite M14 DM000566 N. A. Conjugation - Conjugation 3 [8]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR000903 Efavirenz 8-hydroxy-efavirenz Oxidation - Hydroxylation CYP3A4 ... [5], [3], [6], [7]
MR000904 Efavirenz Efavirenz metabolite M5 Oxidation - Hydroxylation Unclear [8]
MR000905 Efavirenz Efavirenz metabolite M2 Conjugation - Conjugation UGT [8]
MR000898 8-hydroxy-efavirenz Efavirenz metabolite M8 Oxidation - Hydroxylation Unclear [5], [10], [4]
MR000899 8-hydroxy-efavirenz Efavirenz metabolite M1 Conjugation - Conjugation UGT [8], [9]
MR000901 Efavirenz metabolite M5 Efavirenz metabolite M6 Conjugation - Conjugation SULT [8]
MR000902 Efavirenz metabolite M5 Efavirenz metabolite M7 Conjugation - Conjugation UGT [8]
MR000900 Efavirenz metabolite M8 Efavirenz metabolite M14 Conjugation - Conjugation UGT [8]
⏷ Show the Full List of 8 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[2]
Cytochrome P450 2A6 (CYP2A6) DME0005 Homo sapiens
CP2A6_HUMAN
1.14.14.1
[3]
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[4]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[5]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DME0040 Homo sapiens
UD2B7_HUMAN
2.4.1.17
[3]
References
1 Efavirenz was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 CYP2B6 genotype-dependent inhibition of CYP1A2 and induction of CYP2A6 by the antiretroviral drug efavirenz in healthy volunteers. Clin Transl Sci. 2019 Nov;12(6):657-666.
3 Biotransformation of Efavirenz and Proteomic Analysis of Cytochrome P450s and UDP-Glucuronosyltransferases in Mouse, Macaque, and Human Brain-Derived In Vitro Systems. Drug Metab Dispos. 2023 Apr;51(4):521-531. doi: 10.1124/dmd.122.001195.
4 Evaluation of CYP2B6 induction and prediction of clinical drug-drug interactions: considerations from the IQ consortium induction working group-an industry perspective. Drug Metab Dispos. 2016 Oct;44(10):1720-30.
5 Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and phenobarbital. J Clin Pharmacol. 2004 Nov;44(11):1273-81.
6 Liver Cirrhosis Affects the Pharmacokinetics of the Six Substrates of the Basel?Phenotyping Cocktail Differently. Clin Pharmacokinet. 2022 Jul;61(7):1039-1055. doi: 10.1007/s40262-022-01119-0.
7 Instability of Efavirenz Metabolites Identified During Method Development and Validation. J Pharm Sci. 2021 Oct;110(10):3362-3366. doi: 10.1016/j.xphs.2021.06.028.
8 Clinical pharmacokinetics and drug-drug interactions of Elbasvir/Grazoprevir. Eur J Drug Metab Pharmacokinet. 2018 Oct;43(5):509-531.
9 The Activity of Members of the UDP-Glucuronosyltransferase Subfamilies UGT1A and UGT2B is Impaired in Patients with Liver Cirrhosis. Clin Pharmacokinet. 2023 Jun 16. doi: 10.1007/s40262-023-01261-3.
10 Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218.

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