Targeting Lymphoid Malignancies with Small Molecule Inhibitors of Pro-Survival Bcl-2 Proteins.
Andrew W Roberts, Andrew Wei, Mark F van Delft, Kylie D Mason, Jerry M Adams, David CS Huang
Blood | American Society of Hematology | Published : 2005
Abstract As overactivity of pro-survival Bcl-2 proteins promotes neoplasia and enhances resistance of malignant cells to cytotoxic therapies, a promising approach for incurable lymphoid tumors is to directly target the pro-survival proteins. One approach is to mimic their physiological antagonists, the BH3-only proteins. We initially determined which of the diverse BH3-only proteins would be optimal to mimic. The interactions of the BH3 domains of this family with a groove on the Bcl-2-like proteins have been considered promiscuous. However, we found that the interactions between eight BH3 peptides and five Bcl-2-like proteins varied over 10,000 fold in affinity, and that only..View full abstract