Acalabrutinib
- ACP-196
- Optical Purity: Optically pure
- Soluble in DMSO
- MF: C26H23N7O2
- MW: 465.51
Description
Acalabrutinib is a second-generation irreversible inhibitor of BTK (Bruton's tyrosine kinase). The optically pure Acalabrutinib potently inhibits BTK activity with an IC50 of 3 nM (enzymatic assay) and EC50 of 8 nM (human whole-blood CD69 B cell activation assay). Comparing with the first-generation BTK inhibitor Ibrutinib, Acalabrutinib is more selective. The improved selectivity is largely attributed to the reduced intrinsic reactivity of electrophile (Acalabrutinib’s Propiolamide vs Ibrutinib’s acrylamide). As a result, Acalabrutinib was shown to have improved target specificity and in vivo coverage, thus better therapeutic indexes, over Ibrutinib. It displays minimal, or no activities against off-target kinases such as ITK, EGFR, ERBB2, ERBB4, JAK3, BLK, FGR, FYN, HCK, LCK, LYN, SRC, and YES1.
More Information
| Parent CAS No. | 1420477-60-6 |
|---|---|
| Chemical Name | (S)-4-(8-amino-3-(1-but-2-ynoylpyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide |
| extra_info | Sold in collaboration with Chemietek |
| SMILES | N12C([C@H]3N(C(C#CC)=O)CCC3)=NC(C3C=CC(C(NC4N=CC=CC=4)=O)=CC=3)=C1C(N)=NC=C2 |&1:2,r| |
| MFCD | N.A. |
| InChi | N.A. |
| InChiKey | N.A. |
| CID | N.A. |
| Short Description | BTK inhibitor |
References
- JC Byrd et al. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jan 28;374(4):323-32.
- T Covey et al. ACP-196: a novel covalent Bruton’s tyrosine kinase (Btk) inhibitor with improved selectivity and in vivo target coverage in chronic lymphocytic leukemia (CLL) patients. Cancer Res. 2015;75 (15 Supplement): Abstact 2596.
