title: Cyclopeptide Smac mimetics as antagonists of IAP proteins.
abstract: Two cyclopeptidic Smac mimetics, 2 and 3, were designed and synthesized. These two compounds bind to XIAP and cIAP-1/2 with low nanomolar affinities, and restore the activities of caspase-9 and caspase-3/-7 inhibited by XIAP. Compound 2 potently inhibits cancer cell growth and is 5-8 times more potent than the initial lead compound.
authors.affiliation: Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Sun
authors.forename: Liu
authors.initials: L
authors.lastname: Liu
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Lu
authors.forename: Su
authors.initials: S
authors.lastname: Qiu
authors.forename: Chao-Yie
authors.initials: CY
authors.lastname: Yang
authors.forename: Han
authors.initials: H
authors.lastname: Yi
authors.forename: Shaomeng
authors.initials: S
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051034:Inhibitor of Apoptosis Proteins; D009842:Oligopeptides; D010456:Peptides, Cyclic; C551141:SM 162; C532637:SMAC peptide; D014230:Triazoles; D051636:X-Linked Inhibitor of Apoptosis Protein; D053148:Caspase 3; D053179:Caspase 7; D053453:Caspase 9