Buparlisib Hydrochloride is an inhibitor of pan-class I PI3K (IC50: 52 nM/166 nM/116 nM/262 nM for p110α/p110β/p110δ/p110γ, respectively).

NVP-BKM120 shows lower potency against class III and class IV PI3K's, where 2, 5, >5, and >25 μM biochemical activity is observed for inhibition of VPS34, mTOR, DNAPK, and PI4K, respectively. Buparlisib causes multiple myeloma (MM) cell apoptosis in both dose- and time-dependent manners. Buparlisib has 50-300 nM activity for class I PI3K's, including the most common p110α mutants. Buparlisib ( ≥10 μM) induces significant apoptosis in all tested MM cell lines at 24 h (P<0.05, compares with control). Buparlisib (10 μM; 24-h) treatment is chosen in the following experiments if not stated otherwise. Buparlisib treatment causes dose-dependent growth inhibition in all tested MM cell lines. Buparlisib IC50 varies among tested MM cells. At 24 h treatment, IC50 for ARP-1, ARK, and MM.1R is between 1 and 10 μM, while IC50 for MM.1S is <1 μM, and IC50 for U266 is between 10 and 100 μM. Buparlisib treatment results in MM cell growth inhibition and apoptosis in a dose- and time-dependent manners[1][2].

Buparlisib (p.o.; 3, 10, 30, 60, and 100 mg/kg) results in a dose-dependent modulation of pAKTSer473, in A2780 xenograft tumors. Mice receiving Buparlisib (5 μM per kg per day for 15 days) treatment has significantly smaller tumor burdens as compared with control mice, which are measured as tumor volume (P<0.05) and level of circulating human kappa chain (P<0.05). Buparlisib treatment significantly prolongs the survival of tumor-bearing mice (P<0.05). Partial inhibition of pAKTSer473 is observed at 3 and 10 mg/kg, and near-complete inhibition is observed at doses of 30, 60, or 100 mg/kg, respectively. Inhibition of pAKT (normalized to total AKT) tracked well with both plasma and tumor drug exposure[1][2].