期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 60, 期 11, 页码 4611-4625出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.6b01877
关键词
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XIAP and cIAP1 are members of the inhibitor of apoptosis protein (IAP) family and are key regulators of anti-apoptotic and pro-survival signaling pathways. Over expression Of IAPs occurs in various cancers and has been associated with tumor progression and resistance to treatment. Structure-based drug design (SBDD) guided by structural information from X-ray crystallography, computational studies, and NMR solution conformational analysis was successfully applied to.a fragment-derived lead resulting, in AT-IAP, a potent, orally bioavailable, dual antagonist of XIAP and cIAP1 and a structurally novel chemical probe for LAP biology.
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