ABT-263

Overexpression of the prosurvival Bcl-2 family members (Bcl-2,Bcl-xL,and Mcl-1) is commonly associated with tumor maintenance, progression, and chemoresistance. Binding affinities were determined with competitive fluorescence polarization assays and a time-resolved fluorescence resonance energy transfer assay (Ki’s of <1 nmol/L for Bcl-2, Bcl-xL, and Bcl-w). The oral bioavailability of ABT-263 in preclinical animal models is 20% to 50%, depending on formulation.[1]A wide range of SCLC cellular activity was observed with ABT-263 having a 50% growth inhibition (EC50) of 110 nmol/L against the most sensitive line (H146), whereas its activity in the least sensitive line (H82) resulted in an EC50 at 22 μmol/L. In all cell lines where the EC50 was <1 μmol/L, ABT-263 was more potent than its enantiomer by a factor of >20.