tcsc0711 Dactolisib (Tosylate)

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

IC50 & Target: IC50: 4nM (PI3Kα), 75 nM (PI3Kβ), 7 nM (PI3Kγ), 5 nM (PI3Kδ)^[1]


mTORC1, mTORC2^[1]

In Vitro: NVP-Dactolisib (BEZ235) is an imidazo[4,5-c]quinoline derivative that inhibits PI3K and mTOR kinase activity by binding to the ATP-binding cleft of these enzymes. The IC₅₀s for PI3Kα, β, γ, δ are 4, 75, 7, 5 nM, respectively. It is also found to be as active against the mutant PI3Kα^E545K or PI3Kα^H1047R with IC₅₀s of 5.7 and 4.6 nM, respectively. In human tumor cell lines, it is able to effectively and specifically block the dysfunctional activation of the PI3K pathway, inducing G1 arrest. PTEN-null cell lines PC3M and U87MG shows a dose-dependent reduction in cell proliferation when treated with increasing concentrations of NVP-Dactolisib (BEZ235), with an average GI₅₀ of 10 to 12 nM^[1].

In Vivo: NVP-Dactolisib (BEZ235) is well tolerated, displays disease stasis when administered orally, and enhances the efficacy of other anticancer agents. At a dose of 50 mg/kg, NVP-Dactolisib (BEZ235) appears rapidly in plasma with a C_max of 1.68 μM at 0.5 h and a C_24h of 0.03 μM^[1].