Acalisib (GS-9820)

Background:

Acalisib (GS-9820) is a potent and selective inhibitor of PI3Kδ with IC50 value of 12.7 nM [1].

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that phosphorylating the 3’-hydroxyl group of phosphatidylinositol-4,5-bisphosphate (PIP2) to produce phosphatidylinositol-3,4,5-trisphosphate (PIP3). PI3Ks plays important roles in cell proliferation, survival, differentiation and metabolism. PI3Kδ plays an important role in inflammation, immune function, cell migration and vesicle trafficking, and is highly expressed in cells of hematopoietic origin [1].

Acalisib (GS-9820) is a potent and selective PI3Kδ inhibitor. GS-9820 inhibited PI3Kα, β, γ and δ with IC50 values of 5441, 3377, 1389 and 12.7 nM, respectively. In fibroblasts, GS-9820 inhibited PDGF- and LPA-induced pAkt with IC50 values of 11,585 and 2,069 nM respectively, which were through PI3Kα and PI3Kβ. In basophils, GS-9820 inhibited FcεRI PI3Kδ_x0001_- and fMLP PI3Kγ-mediated CD63 expression with EC50 values of 14 nM and 2,065 nM, respectively. In isolated rat osteoclasts, GS-9820 induced prompt retraction of lamellipodia by 65-75% within 10-15 min. GS-9820 also significantly reduced the incidence of F-actin belts and inhibited osteoclast survival stimulated by RANKL [1].

Reference:
[1].  Shugg RP, Thomson A, Tanabe N, et al. Effects of isoform-selective phosphatidylinositol 3-kinase inhibitors on osteoclasts: actions on cytoskeletal organization, survival, and resorption. J Biol Chem, 2013, 288(49): 35346-35357.