acalabrutinib   Click here for help

GtoPdb Ligand ID: 8912

Synonyms: ACP-196 | Calquence® | Example 6 [US20140155385 A1] [2]
Approved drug PDB Ligand Immunopharmacology Ligand
acalabrutinib is an approved drug (FDA (2017), EMA (2020))
Compound class: Synthetic organic
Comment: Acalabrutinib is an orally available second-generation, selective and irreversible inhibitor of Bruton tyrosine kinase (BTK) [6], being investigated for its potential antineoplastic activity (in multiple haematologic malignancies and solid tumours), as well as a potential therapy for rheumatoid arthritis. Acalabrutinib covalently bonds to Cysteine-481 in BTK.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 118.51
Molecular weight 465.19
XLogP 4.09
No. Lipinski's rules broken 0
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Canonical SMILES CC#CC(=O)N1CCCC1c1nc(c2n1ccnc2N)c1ccc(cc1)C(=O)Nc1ccccn1
Isomeric SMILES CC#CC(=O)N1CCC[C@H]1c1nc(c2n1ccnc2N)c1ccc(cc1)C(=O)Nc1ccccn1
InChI 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
Immunopharmacology Comments
Pharmacological inhibition of BTK prevents the activation of B cells and BTK-mediated activation of downstream survival pathways. This leads to inhibition of the growth of malignant B cells overexpressing BTK.
Immunopharmacology Disease
Disease X-Refs Comment References
Rheumatoid arthritis Disease Ontology: DOID:7148
OMIM: 180300
Phase 2 clinical trial in RA completed (NCT02387762)
B-cell chronic lymphocytic leukemia OMIM: 151400
Orphanet: ORPHA67038
Phase 3 clinical candidate for CLL.
Mantle cell lymphoma Disease Ontology: DOID:0050746
Orphanet: ORPHA52416
Approved drug for MCL patients who have received at least one prior therapy. 7