title: Bcl-2 family of proteins as drug targets for cancer chemotherapy: the long way of BH3 mimetics from bench to bedside.
abstract: Bcl-2 proteins are key determinants in the life-death balance. In recent years, proteins in this family have been identified as drug targets in the design of new anti-tumor therapies. Advances in the knowledge of the mechanism of action of anti-apoptotic and pro-apoptotic members of the Bcl-2 family have enabled the development of the so-called 'BH3 mimetics'. These compounds act by inhibiting anti-apoptotic proteins of the family, imitating the function of the BH3-only subset of pro-apoptotic members. Combinations of BH3-mimetics with anti-tumor drugs are being evaluated in both preclinical models and clinical trials. Recent advances in these approaches will be reviewed.
authors.affiliation: Department of Biochemistry, Molecular and Cell Biology, IIS, University of Zaragoza, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Vela
authors.affiliation: Department of Biochemistry, Molecular and Cell Biology, IIS, University of Zaragoza, Spain. Electronic address: imarzo@unizar.es.
authors.forename: Isabel
authors.initials: I
authors.lastname: Marzo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051023:BH3 Interacting Domain Death Agonist Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D040761:Biomimetic Materials / Q000008:administration & dosage / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000639:trends*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: ABT-199 (PubChem CID: 49846579); ABT-737 (PubChem CID: 11228183); Gossypol (PubChem CID: 3503); Navitoclax (PubChem CID: 24978538); Obatoclax (PubChem CID: 16681698)