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

General Information of Drug (ID: DR1315)
Drug Name
Ponatinib hydrochloride
Synonyms
Ponatinib (AP24534); Ponatinib (HCl salt); Ponatinib HCl; Ponatinib Mono-hydrochloride; Ponatinib hydrochloride; Ponatinib hydrochloride [USAN]; 1114544-31-8; 96R6PU3D8J; AOB3899; AP 24534 hydrochloride; AP-24534 HCl; AP24534 HCL; AP24534 Hydrochloride; AS-16772; BCP10906; BWTNNZPNKQIADY-UHFFFAOYSA-N; C29H28ClF3N6O; CHEMBL2105708; D09951; DTXSID50149655; MFCD17215406; Ponatinib hydrochloride (JAN/USAN); SCHEMBL15798559; UNII-96R6PU3D8J; Y1466; Iclusig (TN); 3-(Imidazo[1,2-B]pyridazin-3-Ylethynyl)-4-Methyl-N-{4-[(4-Methylpiperazin-1-Yl)methyl]-3-(Trifluoromethyl)phenyl}benzamide; 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide; 4340891KFS; 943319-70-8; AP 24534; AP-24534; AP24534; AP24534(Ponatinib); C29H27F3N6O; CHEBI:78543; CHEMBL1171837; UNII-4340891KFS; PONATINIB
Indication Acute lymphoblastic leukemia [ICD11: 2B33] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 569 Topological Polar Surface Area 65.8
Heavy Atom Count 40 Rotatable Bond Count 6
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 8
Cross-matching ID
PubChem CID
46908927
CAS Number
1114544-31-8
TTD Drug ID
D0H0EQ
Formula
C29H28ClF3N6O
Canonical SMILES
CC1=C(C=C(C=C1)C(=O)NC2=CC(=C(C=C2)CN3CCN(CC3)C)C(F)(F)F)C#CC4=CN=C5N4N=CC=C5.Cl
InChI
1S/C29H27F3N6O.ClH/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37;/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39);1H
InChIKey
BWTNNZPNKQIADY-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
AP24567 DM002889
24826880
Oxidation - N-Demethylation 1 [3] , [6] , [7]
AP24592 DM002890
46838908
Hydrolysis - Amide Hydrolysis 1 [6]
AP24600 DM002891
58945624
Hydrolysis - Amide Hydrolysis 1 [6]
Ponatinib metabolite M3 DM002892
86292683
Oxidation - Oxidtive Deamination 1 [7]
Ponatinib metabolite M4 DM002893
129851393
Oxidation - Oxygenation 2 [7]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR002083 Ponatinib hydrochloride AP24567 Oxidation - N-Demethylation CYP3A4 ... [3], [6], [7]
MR002084 Ponatinib hydrochloride AP24592 Hydrolysis - Amide Hydrolysis Unclear [6]
MR002085 Ponatinib hydrochloride AP24600 Hydrolysis - Amide Hydrolysis Unclear [6]
MR002086 Ponatinib hydrochloride Ponatinib metabolite M3 Oxidation - Oxidtive Deamination Unclear [7]
MR002082 Ponatinib metabolite M3 Ponatinib metabolite M4 Oxidation - Oxygenation Unclear [7]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A1 (CYP1A1) DME0006 Homo sapiens
CP1A1_HUMAN
1.14.14.1
[2]
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[2]
Cytochrome P450 1B1 (CYP1B1) DME0023 Homo sapiens
CP1B1_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[2]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[3]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[4]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[5]
⏷ Show the Full List of 7  DME(s)
References
1 Ponatinib Hydrochloride was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Novel Pathways of Ponatinib Disposition Catalyzed By CYP1A1 Involving Generation of Potentially Toxic Metabolites J Pharmacol Exp Ther. 2017 Oct;363(1):12-19. doi: 10.1124/jpet.117.243246.
3 Novel pathways of ponatinib disposition catalyzed by CYP1A1 involving generation of potentially toxic metabolites. J Pharmacol Exp Ther. 2017 Oct;363(1):12-19.
4 Evaluation of the effect of multiple doses of rifampin on the pharmacokinetics and safety of ponatinib in healthy subjects. Clin Pharmacol Drug Dev. 2015 Sep;4(5):354-60.
5 Potential of ponatinib to treat chronic myeloid leukemia and acute lymphoblastic leukemia. Onco Targets Ther. 2013 Aug 20;6:1111-8.
6 Absorption, metabolism, and excretion of [(14)C]ponatinib after a single oral dose in humans Cancer Chemother Pharmacol. 2017 Mar;79(3):507-518. doi: 10.1007/s00280-017-3240-x.
7 In vitro metabolites characterization of ponatinib in human liver microsomes using ultra-high performance liquid chromatography combined with Q-Exactive-Orbitrap tandem mass spectrometry Biomed Chromatogr. 2020 Jun;34(6):e4819. doi: 10.1002/bmc.4819.

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