Hot Sell Small Molecular API Bkm120 (CAS# 944396-07-0)

Description 

BKM120 (NVP-BKM120, Buparlisib) is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM in cell-free assays, respectively. Reduced potency against VPS34, mTOR, DNAPK, with little activity to PI4Kβ. Phase 2.

BKM120 is not sensitive to Class III and Class IV PI3K's or PI4K. NVP-BKM120 shows great antiproliferation activity to PI3K deregulated cell lines including A2780, U87MG, MCF7 and DU145 with GI50 of 0.1-0.7 nM.  BKM120 induces multiple myeloma cells (ARP1, ARK, MM.1S, MM1.R and U266) apoptosis, which results in increased G1-phase cells and decreased S-phase cells. BKM120 induced CD138+ primary MM cell apoptosis and has significant lower cytotoxicity toward CD138 stromal cells. BKM120 exposure could cause upregulation of BimS and downregulation of XIAP.  BKM120 demonstrates antiproliferative activity in human gastric cancer cell lines by decreasing mTOR downstream signaling. BKM120 could increase either p-ERK or p-STAT3 in KRAS mutant gastric cancer cells. Combination with STAT3 blockade, BKM120 shows a synergism in cells harboring mutated KRAS by inducing apoptosis, but not in KRAS wild-type cells.  A recent study shows that BKM120 shows differential forms of cell death on the basis of p53 status of the cells with p53 wild-type cells undergoing apoptotic cell death and p53 mutant/deleted cells having a mitotic catastrophe cell death. BKM120 mediates mitotic catastrophe mainly through Aurora B kinase. 

 

 

Application

The effect of the pan-PI3K inhibition, mediated by increased concentrations of buparlisib on MM cell survival was tested by MTT assay. Buparlisib induced cell toxicity after 48 hr treatment in all MM cell lines tested; with an IC50 between 0.5 and 1 μM. In addition, buparlisib decreased the activation of signaling proteins downstream of PI3K including pAkt, pS6R, pP70S6K, and p-mTOR in MM.1S cells in a dose dependent manner. 

Treatment of mice with buparlisib significantly decreased the rate of tumor progression compared with the vehicle treated group, as shown in representative images of the BLI and quantification of the BLI. These results were further confirmed by fluorescence microscopy, showing that the number of MM.1S- GFP+/luc+ cells present in the BM of mice treated with buparlisib decreased significantly compared with those present in the BM of mice treated with vehicle, as shown in representative images of immunofluorescence. 

 

Description 

BKM120 (NVP-BKM120, Buparlisib) is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM in cell-free assays, respectively. Reduced potency against VPS34, mTOR, DNAPK, with little activity to PI4Kβ. Phase 2.

BKM120 is not sensitive to Class III and Class IV PI3K's or PI4K. NVP-BKM120 shows great antiproliferation activity to PI3K deregulated cell lines including A2780, U87MG, MCF7 and DU145 with GI50 of 0.1-0.7 nM.  BKM120 induces multiple myeloma cells (ARP1, ARK, MM.1S, MM1.R and U266) apoptosis, which results in increased G1-phase cells and decreased S-phase cells. BKM120 induced CD138+ primary MM cell apoptosis and has significant lower cytotoxicity toward CD138 stromal cells. BKM120 exposure could cause upregulation of BimS and downregulation of XIAP.  BKM120 demonstrates antiproliferative activity in human gastric cancer cell lines by decreasing mTOR downstream signaling. BKM120 could increase either p-ERK or p-STAT3 in KRAS mutant gastric cancer cells. Combination with STAT3 blockade, BKM120 shows a synergism in cells harboring mutated KRAS by inducing apoptosis, but not in KRAS wild-type cells.  A recent study shows that BKM120 shows differential forms of cell death on the basis of p53 status of the cells with p53 wild-type cells undergoing apoptotic cell death and p53 mutant/deleted cells having a mitotic catastrophe cell death. BKM120 mediates mitotic catastrophe mainly through Aurora B kinase. 

 

 

Application

The effect of the pan-PI3K inhibition, mediated by increased concentrations of buparlisib on MM cell survival was tested by MTT assay. Buparlisib induced cell toxicity after 48 hr treatment in all MM cell lines tested; with an IC50 between 0.5 and 1 μM. In addition, buparlisib decreased the activation of signaling proteins downstream of PI3K including pAkt, pS6R, pP70S6K, and p-mTOR in MM.1S cells in a dose dependent manner. 

Treatment of mice with buparlisib significantly decreased the rate of tumor progression compared with the vehicle treated group, as shown in representative images of the BLI and quantification of the BLI. These results were further confirmed by fluorescence microscopy, showing that the number of MM.1S- GFP+/luc+ cells present in the BM of mice treated with buparlisib decreased significantly compared with those present in the BM of mice treated with vehicle, as shown in representative images of immunofluorescence.