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

General Information of Drug (ID: DR3459)
Drug Name
ABL001
Synonyms
asciminib; ABL-001; 1492952-76-7; Asciminib free base; ABL001-NX; UNII-L1F3R18W77; L1F3R18W77; NVP-ABL001; (R)-N-(4-(Chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)nicotinamide; 1492952-76-7 (free base); N-[4-[chloro(difluoro)methoxy]phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-5-yl)pyridine-3-carboxamide; Asciminib [USAN]; Asciminib (ABL001); Asciminib (USAN/INN); GTPL8962; CHEMBL4208229; SCHEMBL15388306; TQP0925; EX-A3030; BDBM50459091; NSC789925; s8555; ZINC150275965; CCG-269232; CS-7655; DB12597; NSC-789925; SB18878; BS-15538; HY-104010; D11403; Q27074535; (R)-N-(4-(Chloro difluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)nicotinamide; AY7
Indication Chronic myelogenous leukaemia [ICD11: 2A20] Phase 3 [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 449.8 Topological Polar Surface Area 103
Heavy Atom Count 31 Rotatable Bond Count 6
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 8
Cross-matching ID
PubChem CID
72165228
CAS Number
1492952-76-7
TTD Drug ID
DSHT18
Formula
C20H18ClF2N5O3
Canonical SMILES
C1CN(C[C@@H]1O)C2=C(C=C(C=N2)C(=O)NC3=CC=C(C=C3)OC(F)(F)Cl)C4=CC=NN4
InChI
InChI=1S/C20H18ClF2N5O3/c21-20(22,23)31-15-3-1-13(2-4-15)26-19(30)12-9-16(17-5-7-25-27-17)18(24-10-12)28-8-6-14(29)11-28/h1-5,7,9-10,14,29H,6,8,11H2,(H,25,27)(H,26,30)/t14-/m1/s1
InChIKey
VOVZXURTCKPRDQ-CQSZACIVSA-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
ABL001 Metabolite M45 DM019167 N. A. Unclear - Unclear 1 [4]
ABL001 Metabolite M8 DM019165 N. A. Hydrolysis - Hydrolysis 1 [4]
Asciminib metabolite M10 DM004995 N. A. Oxidation - O-dealkylation 1 [4]
Asciminib metabolite M27.5 DM005002 N. A. Conjugation - Glucuronidation 1 [4]
Asciminib metabolite M29.5 DM005000 N. A. Oxidation - Oxidationn ring opening 1 [4]
Asciminib metabolite M30.5 DM004997 N. A. Conjugation - Glucuronidation 1 [4]
Asciminib metabolite M37 DM004993 N. A. Oxidation - Oxidationn ring opening 1 [4]
Asciminib metabolite M39 DM005001 N. A. Oxidation - Oxidationn ring opening 1 [4]
Asciminib metabolite M44 DM004999 N. A. Oxidation - Oxidationn 1 [4]
Asciminib metabolite M43.3 DM004994 N. A. Unclear 2 [4]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR005416 ABL001 Asciminib metabolite M37 Oxidation - Oxidationn ring opening CYP3A4 [4]
MR005419 ABL001 Asciminib metabolite M10 Oxidation - O-dealkylation Unclear [4]
MR005421 ABL001 Asciminib metabolite M30.5 Conjugation - Glucuronidation UGT2B7 ... [4]
MR005423 ABL001 Asciminib metabolite M44 Oxidation - Oxidationn Unclear [4]
MR005424 ABL001 Asciminib metabolite M29.5 Oxidation - Oxidationn ring opening Unclear [4]
MR005425 ABL001 Asciminib metabolite M39 Oxidation - Oxidationn ring opening Unclear [4]
MR005426 ABL001 Asciminib metabolite M27.5 Conjugation - Glucuronidation Unclear [4]
MR011633 ABL001 ABL001 Metabolite M8 Hydrolysis - Hydrolysis Unclear [4]
MR011635 ABL001 ABL001 Metabolite M45 Unclear - Unclear Unclear [4]
MR005417 Asciminib metabolite M37 Asciminib metabolite M43.3 Unclear Unclear [4]
⏷ Show the Full List of 10 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[2]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DME0041 Homo sapiens
UD13_HUMAN
2.4.1.17
[3]
UDP-glucuronosyltransferase 1A4 (UGT1A4) DME0048 Homo sapiens
UD14_HUMAN
2.4.1.17
[3]
UDP-glucuronosyltransferase 2B17 (UGT2B17) DME0066 Homo sapiens
UDB17_HUMAN
2.4.1.17
[3]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DME0040 Homo sapiens
UD2B7_HUMAN
2.4.1.17
[2]
References
1 ClinicalTrials.gov (NCT03106779) Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs. U.S. National Institutes of Health.
2 Pharmacokinetics of asciminib in the presence of CYP3A or P-gp inhibitors, CYP3A inducers, and acid-reducing agents
3 Pharmacokinetic drug interactions of asciminib with the sensitive cytochrome P450 probe substrates midazolam, warfarin, and repaglinide in healthy participants
4 Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects

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