(+)-Apogossypol

(+)-Apogossypol is a pan-BCL-2 antagonist. (+)-Apogossypol binds to Mcl-1, Bcl-2 and Bcl-xL with EC₅₀s of 2.6, 2.8 and 3.69 µM, respectively. IC50 & Target: EC50: 2.60 µM (Mcl-1), 2.80 µM (Bcl-2), 3.69 µM (Bcl-xL)^[1]
Kd: 1.70 µM (Bcl-xL)^[1] In Vitro: In agreement with NMR binding and fluorescence polarization assays (FPAs) data, (+)-Apogossypol displays potent binding affinity to Bcl-xL with K_d values of 1.7 µM^[1].To investigate the inhibitory effects of (+)-Apogossypol and Gossypol on LNCaP cell survival, the MTT assay is performed. The results demonstrate that (+)-Apogossypol inhibits the proliferation of LNCaP cells in a time- and dose-dependent manner, in a similar way with Gossypol. The concentration for 50% inhibition (IC₅₀) on LNCaP cells within ~72 h is 9.57 μM, while the IC₅₀ of Gossypol on LNCaP cells is 10.35 μM^[2]. In Vivo: Due to its modified structure, (+)-Apogossypol is expected to exhibit lower toxicity while maintaining the significant anti-growth and anti-tumor activities in vitro, similar to those of Gossypol. The anti-cancer effect of (+)-Apogossypol is evaluated in mice bearing subcutaneous LNCaP cell xenografts. The tumor growth is monitored and measured by a caliper and balance. The survival rate of the mice is notably improved by (+)-Apogossypol. Of note, the tumor sizes are also markedly decreased by (+)-Apogossypol treatment (P<0.01)^[2].