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

General Information of Drug (ID: DR0031)
Drug Name
Acalabrutinib
Synonyms
Acalabrutinib; Acalabrutinib (ACP-196); Acalabrutinib (JAN/USAN/INN); Acalabrutinib [INN]; Acalabrutinib [USAN:INN]; Acalabrutinib(ACP196); Benzamide, 4-(8-amino-3-((2S)-1-(1-oxo-2-butyn-1-yl)-2-pyrrolidinyl)imidazo(1,5-a)pyrazin-1-yl)-N-2-pyridinyl-; Benzamide, 4-[8-amino-3-[(2S)-1-(1-oxo-2-butyn-1-yl)-2-pyrrolidinyl]imidazo[1,5-a]pyrazin-1-yl]-N-2-pyridinyl-; CHEMBL3707348; EX-A881; GTPL8912; I42748ELQW; SCHEMBL14637368; UNII-I42748ELQW; ACP 196; Calquence; Calquence (TN); 1420477-60-6; ACP-196
Indication Mantle cell lymphoma [ICD11: 2A85] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 465.5 Topological Polar Surface Area 119
Heavy Atom Count 35 Rotatable Bond Count 4
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 6
Cross-matching ID
PubChem CID
71226662
CAS Number
1420477-60-6
TTD Drug ID
D09PQZ
Formula
C26H23N7O2
Canonical SMILES
CC#CC(=O)N1CCCC1C2=NC(=C3N2C=CN=C3N)C4=CC=C(C=C4)C(=O)NC5=CC=CC=N5
InChI
1S/C26H23N7O2/c1-2-6-21(34)32-15-5-7-19(32)25-31-22(23-24(27)29-14-16-33(23)25)17-9-11-18(12-10-17)26(35)30-20-8-3-4-13-28-20/h3-4,8-14,16,19H,5,7,15H2,1H3,(H2,27,29)(H,28,30,35)/t19-/m0/s1
InChIKey
WDENQIQQYWYTPO-IBGZPJMESA-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
Acalabrutinib M2 metabolite DM000592
149353030
Oxidation - Amide Hydrolysis; Oxidation 1 [3]
Acalabrutinib M25 metabolite DM000598
156596923
Oxidation - Dehydration; Oxidation 1 [3]
Acalabrutinib M37 metabolite DM000599
146249178
Oxidation - N-Dealkylation 1 [3]
ACP-5134 DM000595
146249179
Other reaction - Hydration 1 [3]
ACP-5530 DM000589
156613872
Conjugation - Glutathione Conjugation 1 [3]
ACP-5825 DM000600
145996809
Oxidation - Hydroxylation 1 [3]
ACP-5862 DM000591
135177281
Oxidation - Oxidation 1 [3] , [4] , [5]
Acalabrutinib M16 metabolite DM000594 N. A. Reduction - Reduction 2 [3]
Acalabrutinib M2 metabolite DM000592
149353030
Oxidation - Amide Hydrolysis; Oxidation 2 [3]
Acalabrutinib M24 metabolite DM000596 N. A. Reduction - Reduction 2 [3]
Acalabrutinib M3 metabolite DM000593
155929046
Oxidation - N-Dealkylation; Oxidation 2 [3]
Acalabrutinib M45 metabolite DM000597
165411987
Reduction - Reduction 2 [3]
ACP-5531 DM000590
156596825
Conjugation - Conjugation 2 [3]
ACP-5461 DM000053 N. A. Oxidation - N-Dealkylation 3 [3]
⏷ Show the Full List of 14  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR000022 Acalabrutinib ACP-5530 Conjugation - Glutathione Conjugation Unclear [3]
MR000023 Acalabrutinib ACP-5862 Oxidation - Oxidation CYP3A4 [3], [4], [5]
MR000024 Acalabrutinib Acalabrutinib M2 metabolite Oxidation - Amide Hydrolysis; Oxidation Unclear [3]
MR000025 Acalabrutinib ACP-5134 Other reaction - Hydration Unclear [3]
MR000026 Acalabrutinib Acalabrutinib M25 metabolite Oxidation - Dehydration; Oxidation Unclear [3]
MR000027 Acalabrutinib Acalabrutinib M37 metabolite Oxidation - N-Dealkylation Unclear [3]
MR000028 Acalabrutinib ACP-5825 Oxidation - Hydroxylation Unclear [3]
MR000020 ACP-5134 Acalabrutinib M24 metabolite Reduction - Reduction Unclear [3]
MR000021 ACP-5134 Acalabrutinib M45 metabolite Reduction - Reduction Unclear [3]
MR000015 ACP-5530 ACP-5531 Conjugation - Conjugation Unclear [3]
MR000017 ACP-5862 Acalabrutinib M2 metabolite Oxidation - Amide Hydrolysis; Oxidation Unclear [3]
MR000018 ACP-5862 Acalabrutinib M3 metabolite Oxidation - N-Dealkylation; Oxidation Unclear [3]
MR000019 ACP-5862 Acalabrutinib M16 metabolite Reduction - Reduction Unclear [3]
MR000016 ACP-5531 ACP-5461 Oxidation - N-Dealkylation Unclear [3]
⏷ Show the Full List of 14 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]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[2]
References
1 Acalabrutinib was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 FDA label of Acalabrutinib. The 2020 official website of the U.S. Food and Drug Administration.
3 Bioavailability, Biotransformation, and Excretion of the Covalent Bruton Tyrosine Kinase Inhibitor Acalabrutinib in Rats, Dogs, and Humans Drug Metab Dispos. 2019 Feb;47(2):145-154. doi: 10.1124/dmd.118.084459.
4 Identification and Characterization of ACP-5862, the Major Circulating Active Metabolite of Acalabrutinib: Both Are Potent and Selective Covalent Bruton Tyrosine Kinase Inhibitors?. J Pharmacol Exp Ther. 2023 Jan;384(1):173-186. doi: 10.1124/jpet.122.001116.
5 Bioequivalence and Relative Bioavailability Studies to Assess a New Acalabrutinib Formulation That Enables Coadministration With Proton-Pump Inhibitors. Clin Pharmacol Drug Dev. 2022 Nov;11(11):1294-1307. doi: 10.1002/cpdd.1153.

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