title: Targeting inhibitor of apoptosis proteins for therapeutic intervention.
abstract: The inhibitors of apoptosis (IAP) proteins have emerged over the last decade as important targets for therapeutic intervention in human malignancies. Overexpression of IAPs has been implicated in cell survival and resistance against stress-induced apoptosis brought on by radiation and/or chemotherapeutics (currently the standard-of-care in a variety of different cancer diseases). In addition, evasion from death receptor-mediated apoptosis and regulation of NF-κB pathways and cell division have also been associated with IAP proteins. Efforts to target IAP proteins in tumors have focused mainly on designing small molecules that mimic the IAP-binding motif of the endogenous IAP antagonist, second mitochondrial activator of caspases. In addition, several other IAP-targeting strategies, including antisense oligonucleotides and transcriptional repression, have also been initiated, with the hope of providing therapeutic benefit to cancer patients.
authors.affiliation: Department of Medicinal Chemistry, Genentech, Inc., South San Francisco, CA 94080, USA.
authors.forename: Chudi
authors.initials: C
authors.lastname: Ndubaku
authors.forename: Frederick
authors.initials: F
authors.lastname: Cohen
authors.forename: Eugene
authors.initials: E
authors.lastname: Varfolomeev
authors.forename: Domagoj
authors.initials: D
authors.lastname: Vucic
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use; D016923:Cell Death / Q000502:physiology; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense