Dactolisib (Tosylate)

1028385-32-1

C37H31N5O4S

H2O : < 0.1 mg/mL (insoluble); DMSO : 34 mg/mL (52.98 mM; Need ultrasonic and warming)

PI3K/Akt/mTOR; PI3K/Akt/mTOR; Autophagy

Dactolisib Tosylate (BEZ235 Tosylate) is a dual PI3K and mTOR kinase inhibitor with IC₅₀ values of 4, 75, 7, 5 nM for PI3Kalpha, beta, gamma, delta, respectively. Dactolisib Tosylate (BEZ235 Tosylate) inhibits mTORC1 and mTORC2. IC50 & Target: IC50: 4nM (PI3Kalpha), 75 nM (PI3Kbeta), 7 nM (PI3Kgamma), 5 nM (PI3Kdelta)^[1]
mTORC1, mTORC2^[1] In Vitro: 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 PI3Kalpha, beta, gamma, delta are 4, 75, 7, 5 nM, respectively. It is also found to be as active against the mutant PI3Kalpha^E545K or PI3Kalpha^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 Dactolisib (BEZ235), with an average GI₅₀ of 10 to 12 nM^[1]. In Vivo: 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, Dactolisib (BEZ235) appears rapidly in plasma with a C_max of 1.68 uM at 0.5 h and a C_24h of 0.03 uM^[1].