Journal
NATURE REVIEWS DRUG DISCOVERY
Volume 7, Issue 12, Pages 989-1000Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nrd2658
Keywords
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Funding
- National Health and Medical Research Council (Australia)
- Leukemia and Lymphoma Society (USA)
- Cancer Council of Victoria
- The Australian Cancer Research Foundation
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Overexpression of members of the BCL-2 family of pro-survival proteins is commonly associated with unfavourable pathogenesis in cancer. The convergence of cytotoxic stress signals on the extended BCL-2 protein family provides the biological rationale for directly targeting this family to induce apoptotic cell death. Recently, several compounds have been described that inhibit the interaction between BCL- 2 family members and their natural ligand, a helical peptide sequence known as the BH3 domain. Here, we review preclinical and clinical data on these compounds, and recommend four criteria that define antagonists of the BCL-2 protein family.
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