title: Inhibitors of the anti-apoptotic Bcl-2 proteins: a patent review.
abstract: BACKGROUND
  The B-cell lymphoma-2 (Bcl-2) family of proteins is central to the regulation of apoptosis, which is vital for proper tissue development and cellular homeostasis. Anti-apoptotic proteins, members of the Bcl-2 family, are an important survival factor for many cancers and their overexpression has been associated with tumor initiation, progression, and resistance to current anticancer therapies. Therefore, strategies seeking to antagonize the function of Bcl-2 anti-apoptotic proteins have been extensively studied for developing a novel cancer therapy.
  
  
  METHODS
  This review covers research and patent literature of the last 15 years dealing with the discovery and development of inhibitors of the Bcl-2 protein family.
  
  
  CONCLUSIONS
  The feasibility of disrupting protein-protein interactions between anti-apoptotic and pro-apoptotic proteins, members of the Bcl-2 family, using peptidomimetics and small-molecule inhibitors has been successfully established. Three small-molecule inhibitors have entered human clinical trials, which will allow the evaluation of this potential therapeutic approach in cancer patients. It will be important to gain a better understanding of pan and selective Bcl-2 inhibitors in order to facilitate future drug design efforts.
authors.affiliation: University of Michigan, Medical School, Department of Pathology, 4510E MSRB I, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Naval
authors.initials: N
authors.lastname: Bajwa
authors.forename: Chenzhong
authors.initials: C
authors.lastname: Liao
authors.forename: Zaneta
authors.initials: Z
authors.lastname: Nikolovska-Coleska
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010330:Patents as Topic; D057786:Peptidomimetics / Q000494:pharmacology; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D057786:Peptidomimetics; D019253:Proto-Oncogene Proteins c-bcl-2; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase