Obatoclax

A potent inhibitor of Bcl-2 family with IC50s of 1-7 uM for Bcl-2, Bcl-XL, Bcl-w, Bcl-B, Mcl-1 and Bfl-1; potently interferes with the direct interaction between MCL-1 and BAK in intact mitochondrial outer membrane and inhibited the association between MCL-1 and BAK in intact cells. (In Vitro) :Obatoclax Mesylate (GX15-070 Mesylate) inhibits BCL-2, BCL-XL, MCL-1, BCL-w, A1, and BCL-b with Ki values≈1-7 μM.Obatoclax Mesylate (50-200 nM; 24-72 hours) induces a dose- and time-dependent reduction of cell numbers in all human colorectal cancer cell lines. In particular, the IC50 of cell proliferation at 72 h are 25.85, 40.69, and 40.01 nM for HCT116, HT-29, and LoVo cells, respectively.Obatoclax Mesylate (400 nM; for 24 hours) induces autophagy in OSCC cells.Obatoclax Mesylate (50-200 nM; for 24 hours) provokes a dose-dependent increase in the G1-phase cell populations.Obatoclax Mesylate (25-200 nM; for 24 hours) indicates a marked drop in cyclin D1 levels as low as 50 nM.Obatoclax Mesylate induces T286 phosphorylation-dependent or -independent cyclin D1 degradation. in HCT116 and LoVo cells, the steady-state levels of p-Cyclin D (T286) began to decline once exposed to obatoclax Mesylate (200 nM; 1, 3, 6, 12, 24 hours) . Obatoclax Mesylate inhibits GSK3β but activates p38MAPK, while barely affecting ERK1/2 activity in HT-29 cells.Obatoclax Mesylate (50, 100, 150, 200, 250, 300, 350, 400, 450 nM) potently inhibits the clonogenic potential of oral cancer cells. (In Vivo) :Obatoclax Mesylate (GX15-070 Mesylate; 1.15-5 mg/kg; intravenously injected; five consecutive days) exhibits potent antitumor activity in xenograft mouse models in a dose-dependent manner.