A66

A66 is a potent and highly selective small molecule inhibitor of the p110α isoform of Class IA phosphoinositide 3-kinase (PI3K). Developed as a pharmacological tool, it binds to the ATP-binding pocket of the p110α catalytic subunit, preventing the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3). A66 exhibits significant selectivity for p110α over other class I PI3K isoforms (p110β, p110δ, and p110γ) and a broad panel of other protein kinases. In preclinical studies, A66 has been used to investigate the specific role of p110α in oncogenic signaling, particularly in cancer models harboring PIK3CA mutations. It has demonstrated the ability to inhibit Akt phosphorylation and reduce cell viability in PIK3CA-mutant endometrial and breast cancer cell lines, while showing minimal effect in PTEN-deficient models that may rely more heavily on the p110β isoform.

Other names

(2S)-N-[5-[(1S)-2,2,2-trifluoro-1-hydroxyethyl]-2-thiazolyl]-2-[[2-methyl-4-pyrimidinyl]amino]-2-(3-pyridinyl)acetamide(S)-N-(5-(2,2,2-trifluoro-1-hydroxyethyl)thiazol-2-yl)-2-((2-methylpyrimidin-4-yl)amino)-2-(pyridin-3-yl)acetamide