A pan-Bcl-2 inhibitor
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].
参考文献:
[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.
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