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

General Information of Drug (ID: DR0843)
Drug Name
Ibrutinib
Synonyms
Ibrutinib; Ibrutinib (PCI-32765); PCI 32765; PCI-32765; PCI-32765 (Ibrutinib); PCI32765; IMBRUVICA; (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one; 1-[(3R)-3-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one; 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one; 1X70OSD4VX; 936563-96-1; A1-01649; CHEBI:76612; CRA-032765; UNII-1X70OSD4VX
Indication Mantle cell lymphoma [ICD11: 2A85] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 440.5 Topological Polar Surface Area 99.2
Heavy Atom Count 33 Rotatable Bond Count 5
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 6
Cross-matching ID
PubChem CID
24821094
PubChem SID
49837088 ; 57132050 ; 123051065 ; 124898784 ; 124898785 ; 136940589 ; 136961336 ; 137472671 ; 152258295 ; 160647134 ; 162202692 ; 163312254 ; 163679284 ; 164045821 ; 164193915 ; 165245631 ; 171572071 ; 172919350 ; 174007139 ; 175267389 ; 176250273 ; 178103494 ; 184611713 ; 184816969 ; 189025882 ; 198993428 ; 215784879 ; 223375297 ; 223485070 ; 223600477 ; 223685684 ; 223704724 ; 224184328 ; 226558356 ; 242585660 ; 247523488 ; 249736825 ; 251971042 ; 252088605 ; 252110183 ; 252160516 ; 252215999 ; 252451849
ChEBI ID
CHEBI:76612
CAS Number
936563-96-1
TTD Drug ID
D09KTS
Formula
C25H24N6O2
Canonical SMILES
C=CC(=O)N1CCCC(C1)N2C3=NC=NC(=C3C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)N
InChI
1S/C25H24N6O2/c1-2-21(32)30-14-6-7-18(15-30)31-25-22(24(26)27-16-28-25)23(29-31)17-10-12-20(13-11-17)33-19-8-4-3-5-9-19/h2-5,8-13,16,18H,1,6-7,14-15H2,(H2,26,27,28)/t18-/m1/s1
InChIKey
XYFPWWZEPKGCCK-GOSISDBHSA-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
Desacryl-Ibrutinib DM004252
154688569
Unclear 1 [3]
PCI-45227 (M37) DM004253
91971609
Multi-steps Reaction - Epoxidation; hydrolyzation 1 [2]
PCI-45741 (M25) DM004247
135390715
Multi-steps Reaction - Dehydrogenation; hydroxylation; reduction; oxidation 1 [2]
PCI-45752 (M34) DM004249
133082586
Unclear 1 [2]
PCI-45773 (M35) DM004245 N. A. Oxidation - Hydrolyzationn 1 [2]
PCI-48303 (M26) DM004237 N. A. Conjugation - Glutathione conjugation 1 [2]
PCI-7503 (M23) DM004251
58223272
Hydrolysis - Hydrolyzation 1 [2]
Ibrutinib Metabolite M17 DM004246 N. A. Oxidation - Hydrolyzationn 2 [4]
Ibrutinib Metabolite M17 DM004246 N. A. Reduction - Reduction 2 [4]
Ibrutinib Metabolite M20 DM004248 N. A. Oxidation - Hydrolyzationn 2 [4]
Ibrutinib Metabolite M24 DM004250 N. A. Multi-steps Reaction - Epoxidation; hydrolyzation 2 [4]
ICGS DM004238 N. A. Unclear 2 [3]
ICYS DM004239 N. A. Unclear 3 [3]
Ibrutinib sulphenic acid DM004243 N. A. Unclear 4 [3]
Ibrutinib-mercapturic acid DM004242 N. A. Unclear 4 [3]
Ibrutinib-S-glucuronide DM004244 N. A. Unclear 4 [3]
Ibrutinib-SH DM004240
126970810
Unclear 4 [3]
S-Methyl-Ibrutinib DM004241 N. A. Unclear 5 [3]
⏷ Show the Full List of 18  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR012946 Ibrutinib PCI-48303 (M26) Conjugation - Glutathione conjugation GSTP1 [2]
MR012954 Ibrutinib PCI-45773 (M35) Oxidation - Hydrolyzationn Unclear [2]
MR012956 Ibrutinib PCI-45741 (M25) Multi-steps Reaction - Dehydrogenation; hydroxylation; reduction; oxidation Unclear [2]
MR012958 Ibrutinib PCI-45752 (M34) Unclear Unclear [2]
MR012961 Ibrutinib PCI-7503 (M23) Hydrolysis - Hydrolyzation Unclear [2]
MR012962 Ibrutinib Desacryl-Ibrutinib Unclear ES [3]
MR012963 Ibrutinib PCI-45227 (M37) Multi-steps Reaction - Epoxidation; hydrolyzation CYP3A4 ... [2]
MR012957 PCI-45741 (M25) Ibrutinib Metabolite M20 Oxidation - Hydrolyzationn Unclear [4]
MR012959 PCI-45752 (M34) Ibrutinib Metabolite M17 Oxidation - Hydrolyzationn Unclear [4]
MR012960 PCI-45752 (M34) Ibrutinib Metabolite M24 Multi-steps Reaction - Epoxidation; hydrolyzation Unclear [4]
MR012955 PCI-45773 (M35) Ibrutinib Metabolite M17 Reduction - Reduction Unclear [4]
MR012947 PCI-48303 (M26) ICGS Unclear GGT5 [3]
MR012948 ICGS ICYS Unclear DPEP1 [3]
MR012949 ICYS Ibrutinib-SH Unclear Unclear [3]
MR012951 ICYS Ibrutinib-mercapturic acid Unclear NATF [3]
MR012952 ICYS Ibrutinib sulphenic acid Unclear Unclear [3]
MR012953 ICYS Ibrutinib-S-glucuronide Unclear UGT1A1 [3]
MR012950 S-Methyl-Ibrutinib S-Methyl-Ibrutinib Unclear TMT1B [3]
⏷ Show the Full List of 18 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[2]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[2]
Dehydropeptidase-I (DPEP1) DME0117 Homo sapiens
DPEP1_HUMAN
3.4.13.19
[3]
Esterases (ES) DMEN229 Homo sapiens Not Available Not Available [3]
Gamma-glutamyltranspeptidase 5 (GGT5) DME0432 Homo sapiens
GGT5_HUMAN
3.4.19.13
[3]
Glutathione S-transferase pi (GSTP1) DME0088 Homo sapiens
GSTP1_HUMAN
2.5.1.18
[2]
N-Acetyl transferases (NATF) DMEN228 Bacteroides fragilis Not Available Not Available [3]
Thiol S-methyltransferase TMT1B (TMT1B) DMEN227 Homo sapiens
TMT1B_HUMAN
2.1.1.9
[3]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[3]
⏷ Show the Full List of 10  DME(s)
References
1 Ibrutinib was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Absorption, metabolism, and excretion of oral 14C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab Dispos. 2015 Feb;43(2):289-97.
3 Extrahepatic metabolism of ibrutinib
4 DrugBank(Pharmacology-Metabolism):Ibrutinib

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