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Sabutoclax is an inhibitor of pan-Bcl-2 family with IC50 values of 0.32, 0.31, 0.20 and 0.62 μM for Bcl-2, Bcl-xL, Mcl-1 and Bfl-1, respectively [1].
Sabutoclax is a derivative of apogossypolone. It showed a high binding affinity to Bcl-xL both in NMR binding assay and in ITC assay, with a Kd value of 0.11μM. Sabutoclax also showed better cell membrane permeability than other apogossypolone derivatives. In PC3 cells, sabutoclax inhibited cell growth with EC50 value of 0.13 μM. In human BP3 cell line, sabutoclax induced cell apoptosis with IC50 value of 0.049 μM. In mice bearing M2182 cancer xenografts, administration of sabutoclax significantly reduced the tumor size. At dose of 5 mg/kg, sabutoclax induced near complete tumor growth suppression [1].
References:[1] Wei J, Stebbins J L, Kitada S, et al. BI-97C1, an optically pure Apogossypol derivative as pan-active inhibitor of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins. Journal of medicinal chemistry, 2010, 53(10): 4166-4176.
Cell lines
PC-3 human prostate cancer cells, H460 human lung cancer cells, BP3 B-cell lymphoma cells, and mouse embryonic fibroblast cells
Reaction Conditions
3 d incubation
Applications
Sabutoclax potently inhibited cell growth of human prostate cancer (3 d), lung cancer (3 d), and lymphoma (1 ~ 2 d) cell lines, with EC50 values of 0.13, 0.56, and 0.049 μM, respectively. In addition, sabutoclax (overnight incubation) showed little cytotoxicity against bax-/-bak-/- mouse embryonic fibroblast cells at 30 μM, while it killed almost 70% wild-type mouse embryonic fibroblast cells at the same concentration.
Animal models
Bcl-2 transgenic mice; human prostate cancer xenografts
Dosage form
42 mg/kg for transgenic mice; 1, 3 or 5 mg/kg for the prostate cancer mouse xenograft model
Administered intraperitoneally
Sabutoclax displayed in vivo efficacy in transgenic mice models and also demonstrated superior single-agent antitumor efficacy in a prostate cancer mouse xenograft model. Therefore, sabutoclax represents a potential drug lead for the development of novel apoptosis-based therapies against cancer.
Note
The technical data provided above is for reference only.
References:
1. Wei J, Stebbins J L, Kitada S, et al. BI-97C1, an optically pure Apogossypol derivative as pan-active inhibitor of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins. Journal of medicinal chemistry, 2010, 53(10): 4166-4176.
