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

General Information of Drug (ID: DR1207)
Drug Name
Osimertinib
Synonyms
Mereletinib; Tagrisso; osimertinib; 1421373-65-0; 3C06JJ0Z2O; AK170511; AZD 9291; AZD-9291; AZD9291; N-(2-((2-(Dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide; N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide; N-[2-[[2-(Dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl]amino]phenyl]-2-propenamide; UNII-3C06JJ0Z2O
Indication Lung cancer [ICD11: 2C25] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 499.6 Topological Polar Surface Area 87.6
Heavy Atom Count 37 Rotatable Bond Count 10
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 7
Cross-matching ID
PubChem CID
71496458
PubChem SID
163477648 ; 182111940 ; 184525804 ; 184525822 ; 184525841 ; 184525860 ; 198967282 ; 210275341 ; 210280989 ; 223366052 ; 223370460 ; 223471425 ; 224657041 ; 226088106 ; 239637404 ; 242060364 ; 249735121 ; 249814472 ; 251910422 ; 252110297 ; 252151380 ; 252160935 ; 252214941 ; 252451374 ; 252551957 ; 252811262
ChEBI ID
CHEBI:90943
CAS Number
1421373-65-0
TTD Drug ID
D0RT2C
Formula
C28H33N7O2
Canonical SMILES
CN1C=C(C2=CC=CC=C21)C3=NC(=NC=C3)NC4=C(C=C(C(=C4)NC(=O)C=C)N(C)CCN(C)C)OC
InChI
1S/C28H33N7O2/c1-7-27(36)30-22-16-23(26(37-6)17-25(22)34(4)15-14-33(2)3)32-28-29-13-12-21(31-28)20-18-35(5)24-11-9-8-10-19(20)24/h7-13,16-18H,1,14-15H2,2-6H3,(H,30,36)(H,29,31,32)
InChIKey
DUYJMQONPNNFPI-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
AZ5104 DM002315
71496460
Unclear 1 [6] , [7] , [8]
AZ7550 DM002316
71496459
Unclear 1 [6] , [7] , [8]
Osimertinib metabolite M1 DM002312
132609257
Unclear 1 [6]
Osimertinib metabolite M17 DM002314 N. A. Unclear 1 [6]
Osimertinib metabolite M18 DM002313 N. A. Unclear 1 [6]
Osimertinib metabolite M2 DM002317
145022764
Unclear 1 [6]
Osimertinib metabolite M8 DM002318 N. A. Unclear 1 [6]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001848 Osimertinib Osimertinib metabolite M1 Unclear Unclear [6]
MR001849 Osimertinib Osimertinib metabolite M18 Unclear Unclear [6]
MR001850 Osimertinib Osimertinib metabolite M17 Unclear Unclear [6]
MR001851 Osimertinib AZ5104 Unclear CYP3A4 ... [6], [7], [8]
MR001852 Osimertinib AZ7550 Unclear CYP3A4 ... [6], [7], [8]
MR001853 Osimertinib Osimertinib metabolite M2 Unclear Unclear [6]
MR001854 Osimertinib Osimertinib metabolite M8 Unclear Unclear [6]
⏷ 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 3A (CYP3A) DMEN065 . Not Available Not Available [3]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[4]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[5]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[6]
References
1 Osimertinib was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 FDA Label of Osimertinib. The 2020 official website of the U.S. Food and Drug Administration.
3 Metabolism and pharmacokinetic study of deuterated osimertinib
4 FDA Approved Drug Products: TAGRISSO (osimertinib) tablets for oral use
5 The Influence of CYP3A4 Genetic Polymorphism and Proton Pump Inhibitors on Osimertinib Metabolism
6 Metabolic Disposition of Osimertinib in Rats, Dogs, and Humans: Insights into a Drug Designed to Bind Covalently to a Cysteine Residue of Epidermal Growth Factor Receptor Drug Metab Dispos. 2016 Aug;44(8):1201-12. doi: 10.1124/dmd.115.069203.
7 Population Pharmacokinetics, Pharmacogenomics, and Adverse Events of Osimertinib and its Two Active Metabolites, AZ5104 and AZ7550, in Japanese Patients with Advanced Non-small Cell Lung Cancer: a Prospective Observational Study. Invest New Drugs. 2023 Feb;41(1):122-133. doi: 10.1007/s10637-023-01328-9.
8 Instability Mechanism of Osimertinib in Plasma and a Solving Strategy in the Pharmacokinetics Study. Front Pharmacol. 2022 Jul 22;13:928983. doi: 10.3389/fphar.2022.928983.

If you find any error in data or bug in web service, please kindly report it to Dr. Yin and Dr. Li.