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Acalabrutinib (Molecule of the Month for September 2017)



Acalabrutinib is a novel experimental anti-cancer drug and a 2nd generation Bruton's tyrosine kinase (BTK) inhibitor developed by Acerta Pharma. It is more potent and selective (fewer side-effects) than ibrutinib, the first-in-class BTK inhibitor. Relative to ibrutinib, acalabrutinib demonstrated higher selectivity and inhibition of the targeted activity of BTK, while having a much greater IC50 or otherwise virtually no inhibition on the kinase activities of ITK, EGFR, ERBB2, ERBB4, JAK3, BLK, FGR, FYN, HCK, LCK, LYN, SRC, and YES1. In addition, in platelets treated with ibrutinib, thrombus formation was clearly inhibited while no impact to thrombus formation was identified relative to controls for those treated with acalabrutinib. These findings strongly suggest an improved safety profile of acalabrutinib with minimized adverse effects relative to ibrutinib.

The interim results of the still on-going first human phase 1/2 clinical trial (NCT02029443) with 61 patients for the treatment of relapsed chronic lymphocytic leukemia (CLL) are encouraging, with a 95% overall response rate demonstrating potential to become a best-in-class treatment for CLL. Notably, a 100% response rate was achieved for those patients which were positive for the 17p13.1 gene deletion - a subgroup of patients that typically results in a poor response to therapy and expected outcomes.

Formal Chemical Name (IUPAC)
4-{8-Amino-3-[(2S)-1-(2-butynoyl)-2-pyrrolidinyl]imidazo[1,5-a]pyrazin-1-yl}-N-(2-pyridinyl)benzamide

References

https://en.wikipedia.org/wiki/Acalabrutinib

Picture of Acalabrutinib 3D model

click on the picture of  Acalabrutinib above to interact
with the 3D model of the
Acalabrutinib structure
(this will open a new browser window)

Picture of Acalabrutinib

C26 H23 N7 O2



Update by Karl Harrison
(Molecule of the Month for September 2017 )

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