Dactolisib Tosylate (BEZ235 Tosylate) is a dual kinase inhibitor targeting PI3K and mTOR, with IC50 values of 4, 75, 7, and 5 nM for PI3Kα, β, γ, and δ, respectively. It also inhibits mTORC1 and mTORC2.

p110β:75 nM, p110α-H1047R:4.6 nM, p110δ:7 nM, p110γ:5 nM, p110α:4 nM, p110α-E545K:5.7 nM, mTOR:20.7 nM

Dactolisib (BEZ235) exhibits IC50 values of 4 nM, 75 nM, 7 nM, and 5 nM against PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ, respectively. Furthermore, it demonstrates significant activity against mutant forms of PI3Kα, specifically PI3KαE545K and PI3KαH1047R, with IC50 values of 5.7 nM and 4.6 nM, respectively. Treatment with increasing concentrations of Dactolisib (BEZ235) leads to a dose-dependent reduction in cell proliferation in PTEN-null cell lines PC3M and U87MG, with an average GI50 ranging from 10 to 12 nM. Notably, in human tumor cell lines, it effectively and specifically blocks the aberrant activation of the PI3K pathway, leading to G1 arrest.[1]

Dactolisib (BEZ235) (50 mg/kg) appears rapidly in plasma with a Cmax of 1.68 μM at 0.5 h and a C24h of 0.03 μM. BEZ235 is well tolerated, and displays disease stasis when administered orally. It enhances the efficacy of other anticancer agents.[1]