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

General Information of Drug (ID: DR3362)
Drug Name
AP26113
Synonyms
1197958-12-5; ALK-IN-1; UNII-3DGD69C6PV; 3DGD69C6PV; CHEMBL3397300; (2-((5-chloro-2-((4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide; 5-Chloro-N~2~-{4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyphenyl}-N~4~-[2-(dimethylphosphoryl)phenyl]pyrimidine-2,4-diamine; 5-chloro-2-N-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyphenyl]-4-N-(2-dimethylphosphorylphenyl)pyrimidine-2,4-diamine; AP26113-analog; Tube723; compound 11q [PMID: 27144831]
Indication Solid tumour/cancer [ICD11: 2A00-2F9Z] Phase 2 [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 529 Topological Polar Surface Area 82.6
Heavy Atom Count 36 Rotatable Bond Count 8
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 8
Cross-matching ID
PubChem CID
57390074
CAS Number
1197958-12-5
TTD Drug ID
D0O9PQ
Formula
C26H34ClN6O2P
Canonical SMILES
CN(C)C1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)NC4=CC=CC=C4P(=O)(C)C)Cl)OC
InChI
InChI=1S/C26H34ClN6O2P/c1-32(2)18-12-14-33(15-13-18)19-10-11-21(23(16-19)35-3)30-26-28-17-20(27)25(31-26)29-22-8-6-7-9-24(22)36(4,5)34/h6-11,16-18H,12-15H2,1-5H3,(H2,28,29,30,31)
InChIKey
OVDSPTSBIQCAIN-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
AP26123 DM001467 N. A. Multi-steps Reaction - N-demethylation; cysteine conjugation 1 [2]
BGB486 DM001470 N. A. Multi-steps Reaction - N-Dealkylation; loss of N-methyl piperazine ring 1 [4]
BGB570 DM001469
68165256
Oxidation - N-Demethylation 1 [4]
BGB598 DM001471 N. A. Oxidation - A-Oxidation 1 [4]
BGB600 DM001468 N. A. Oxidation - A-Hydroxylation 1 [4]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR008510 AP26113 AP26123 Multi-steps Reaction - N-demethylation; cysteine conjugation CYP3A4 ... [2]
MR008511 AP26113 BGB600 Oxidation - A-Hydroxylation Unclear [4]
MR008512 AP26113 BGB570 Oxidation - N-Demethylation Unclear [4]
MR008513 AP26113 BGB486 Multi-steps Reaction - N-Dealkylation; loss of N-methyl piperazine ring Unclear [4]
MR008514 AP26113 BGB598 Oxidation - A-Oxidation Unclear [4]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[3]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[3]
References
1 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. (Ligand id: 7741).
2 Brigatinib: first global approval. Drugs. 2017 Jul;77(10):1131-1135.
3 DrugBank(Pharmacology-Metabolism):AP26113
4 LC-ESI-MS/MS reveals the formation of reactive intermediates in brigatinib metabolism: elucidation of bioactivation pathways

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