Cyclopeptide Smac mimetics as antagonists of IAP proteins.
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.
Sun
Haiying
H
Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Liu
Liu
L
Lu
Jianfeng
J
Qiu
Su
S
Yang
Chao-Yie
CY
Yi
Han
H
Wang
Shaomeng
S
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
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