Obatoclax  (Synonyms: GX15-070)

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].

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

317.38

C₂₀H₁₉N₃O

803712-67-6

固体

Light brown to brown

奥巴克拉

Room temperature in continental US; may vary elsewhere.

• [1]. Or CR, et al. Obatoclax, a Pan-BCL-2 Inhibitor, Targets Cyclin D1 for Degradation to Induce Antiproliferation in Human Colorectal Carcinoma Cells. Int J Mol Sci. 2016 Dec 27;18(1).  [Content Brief]

  [2]. Nguyen M, et al. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19512-7. Epub 2007 Nov 26.  [Content Brief]

  [3]. Sulkshane P, et al. BH3 mimetic Obatoclax (GX15-070) mediates mitochondrial stress predominantly via MCL-1 inhibition and induces autophagy-dependent necroptosis in human oral cancer cells. Oncotarget. 2016 Aug 5;8(36):60060-60079.  [Content Brief]

  [4]. Ehrenkaufer G, et al. Identification of anisomycin, prodigiosin and obatoclax as compounds with broad-spectrum anti-parasitic activity. PLoS Negl Trop Dis. 2020 Mar 20;14(3):e0008150.  [Content Brief]