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

General Information of Drug (ID: DR0125)
Drug Name
Aprepitant
Synonyms
Aprepitant; L 754030; L-754030; MK 0869; MK 869; MK-0869; MK-869; MK0869; aprepitantum; 170729-80-3; 1NF15YR6UY; 5-[[(2R,3S)-2-[(1R)-1-[3,5-BIS(Trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-4-morpholinyl]methyl]-1,2-dihydro-3H-1,2,4-triazol-3-one; 5-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl]-1,2-dihydro-1,2,4-triazol-3-one; CHEBI:499361; CHEMBL1471; Emend; UNII-1NF15YR6UY
Indication Functional nausea/vomiting [ICD11: DD90] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 534.4 Topological Polar Surface Area 75.2
Heavy Atom Count 37 Rotatable Bond Count 6
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 12
Cross-matching ID
PubChem CID
135413536
ChEBI ID
CHEBI:499361
CAS Number
170729-80-3
TTD Drug ID
D0GU4K
Formula
C23H21F7N4O3
Canonical SMILES
CC(C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)OC2C(N(CCO2)CC3=NNC(=O)N3)C4=CC=C(C=C4)F
InChI
1S/C23H21F7N4O3/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)37-20-19(13-2-4-17(24)5-3-13)34(6-7-36-20)11-18-31-21(35)33-32-18/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H2,31,32,33,35)/t12-,19+,20-/m1/s1
InChIKey
ATALOFNDEOCMKK-OITMNORJSA-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
(2R)-2-(4-fluorophenyl)-2-{[(5-oxo-2,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]amino}acetic acid DM000646 N. A. Oxidation - O-Dealkylation 1 [2] , [3]
(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine DM000644
10113945
Oxidation - N-Dealkylation 1 [2] , [3]
1-[3,5-bis(trifluoromethyl)phenyl]ethanone DM000649
121616
Oxidation - N-Demethylation 1 [2] , [3]
5-({[(1R)-1-(4-fluorophenyl)-2-hydroxyethyl]amino}methyl)-2,3-dihydro-1H-1,2,4-triazol-3-one DM000645 N. A. Oxidation - O-Dealkylation 1 [2] , [3]
5-oxo-1,4-dihydro-1,2,4-triazole-3-carbaldehyde DM000648
135985157
Oxidation - N-Dealkylation 1 [2] , [3]
5-{[(2S,3S)-3-(4-fluorophenyl)-2-hydroxymorpholin-4-yl]methyl}-2,4-dihydro-1,2,4-triazol-3-one DM000650
154699529
Oxidation - N-Demethylation 1 [2] , [3]
Aprepitant glucuronide DM000651 N. A. Conjugation - Glucuronidation 1 [4]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR002969 Aprepitant (2S,3R)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine Oxidation - N-Dealkylation CYP3A4 [2], [3]
MR002970 Aprepitant 5-({[(1R)-1-(4-fluorophenyl)-2-hydroxyethyl]amino}methyl)-2,3-dihydro-1H-1,2,4-triazol-3-one Oxidation - O-Dealkylation CYP3A4 ... [2], [3]
MR002971 Aprepitant (2R)-2-(4-fluorophenyl)-2-{[(5-oxo-2,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]amino}acetic acid Oxidation - O-Dealkylation CYP3A4 ... [2], [3]
MR002972 Aprepitant 5-oxo-1,4-dihydro-1,2,4-triazole-3-carbaldehyde Oxidation - N-Dealkylation CYP3A4 ... [2], [3]
MR002973 Aprepitant 1-[3,5-bis(trifluoromethyl)phenyl]ethanone Oxidation - N-Demethylation CYP3A4 ... [2], [3]
MR002974 Aprepitant 5-{[(2S,3S)-3-(4-fluorophenyl)-2-hydroxymorpholin-4-yl]methyl}-2,4-dihydro-1,2,4-triazol-3-one Oxidation - N-Demethylation CYP3A4 ... [2], [3]
MR002975 Aprepitant Aprepitant glucuronide Conjugation - Glucuronidation UGT1A4 [4]
⏷ Show the Full List of 7 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 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[3]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[2]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DME0041 Homo sapiens
UD13_HUMAN
2.4.1.17
[4]
UDP-glucuronosyltransferase 1A4 (UGT1A4) DME0048 Homo sapiens
UD14_HUMAN
2.4.1.17
[4]
UDP-glucuronosyltransferase 1A8 (UGT1A8) DME0064 Homo sapiens
UD18_HUMAN
2.4.1.17
[4]
⏷ Show the Full List of 6  DME(s)
References
1 Aprepitant was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant. Drug Metab Dispos. 2004 Nov;32(11):1287-92.
3 Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients. Cancer Chemother Pharmacol. 2005 Jun;55(6):609-16.
4 In vitro glucuronidation of aprepitant: a moderate inhibitor of UGT2B7 Xenobiotica. 2015;45(11):990-8. doi: 10.3109/00498254.2015.1038743.

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