alexa The challenge of drugging undruggable targets in cancer: lessons learned from targeting BCL-2 family members.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Proteomics & Bioinformatics

Author(s): Verdine GL, Walensky LD

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Abstract The genomic and proteomic revolutions have provided us with an ever-increasing number of mechanistic insights into cancer pathogenesis. Mutated genes and pathologic protein products have emerged as the basis for modern anticancer drug development. With the increasing realization of the importance of disrupting oncogenic protein-protein interaction, new challenges have emerged for classical small molecule and protein-based drug modalities, i.e., the critical need to target flat and extended protein surfaces. Here, we highlight two distinct technologies that are being used to bridge the pharmacologic gap between small molecules and protein therapeutics. With the BCL-2 family of survival proteins as their substrate for intracellular targeting, we conclude that peptide stapling and fragment-based drug discovery show promise to traverse the critical surface features of proteins that drive human cancer. This article was published in Clin Cancer Res and referenced in Journal of Proteomics & Bioinformatics

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