Obatoclax

Obatoclax (GX15-070), a BH3 mimetic, is a pan-BCL-2 family proteins inhibitor with a K_i of 220 nM for BCL-2^[1][2]. Obatoclax induces autophagy-dependent cell death and targets cyclin D1 for proteasomal degradation. Obatoclax has anti-cancer and broad-spectrum antiparasitic activity^[3][4]. In Vitro: Obatoclax (GX15-070) inhibits BCL-2, BCL-XL, MCL-1, BCL-w, A1, and BCL-b with Ki values≈1-7 μM^[2].
Obatoclax (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^[1].
Obatoclax (400 nM; for 24 hours) induces autophagy in OSCC cells^[3].
Obatoclax (50-200 nM; for 24 hours) provokes a dose-dependent increase in the G1-phase cell populations^[1].
Obatoclax (25-200 nM; for 24 hours) indicates a marked drop in cyclin D1 levels as low as 50 nM^[1].
Obatoclax 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 (200 nM; 1, 3, 6, 12, 24 hours). Obatoclax inhibits GSK3β but activates p38 MAPK, while barely affecting ERK1/2 activity in HT-29 cells^[1].
Obatoclax (50, 100, 150, 200, 250, 300, 350, 400, 450 nM) potently inhibits the clonogenic potential of oral cancer cells^[1].
In Vivo: Obatoclax (GX15-070; 1.15-5 mg/kg; intravenously injected; five consecutive days) exhibits potent antitumor activity in xenograft mouse models in a dose-dependent manner^[4].