Targeting Bcl-2 and Bcl-XL with nonpeptidic small-molecule antagonists.
Members of the Bcl-2 family of proteins are crucial regulators of programmed cell death or apoptosis. This family of proteins now includes both anti-apoptotic molecules such as Bcl-2 and Bcl-X(L), and pro-apoptotic molecules such as Bax, Bak, Bid, and Bad. The majority of human cancers are found to have overexpression of Bcl-2, Bcl-X(L), or both. Bcl-2 and Bcl-X(L) may play a critical role in cancer progression. Cancers with high levels of Bcl-2 or Bcl-X(L) or both proteins are resistant to a wide spectrum of chemotherapeutic agents and radiation therapy. Bcl-2 and Bcl-X(L) have become attractive targets for designing new anticancer drugs. Small-molecule inhibitors that are capable of inhibiting the activity of Bcl-2 and Bcl-X(L) may have great therapeutic potential as an entirely new class of anticancer drugs for treating many forms of cancers in which Bcl-2 and/or Bcl-X(L) proteins are overexpressed and for which traditional therapies are ineffective. Design of small-molecule inhibitors of Bcl-2 and Bcl-X(L) is a very new and exciting area for current anticancer drug design and development. In this article we will provide a brief review on the strategy and recent progress in designing small-molecule antagonists targeting Bcl-2 and Bcl-X(L).
Wang
Shaomeng
S
Department of Internal Medicine and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Yang
Dajun
D
Lippman
Marc E
ME
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001665:Binding Sites; D015870:Gene Expression; D019254:Genes, bcl-2; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D011487:Protein Conformation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D051020:bcl-X Protein
D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein