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• W2765642169 abstract "This chapter focuses on potent inhibitor of apoptosis protein (IAP) antagonists that demonstrate cellular penetration and a proven ability to prevent tumor growth. It employs DNA-programmed chemistry (DPC) to generate a library of macrocycles targeted for the BIR domains of intracellular IAP proteins. Screening the library in affinity-based selections against immobilized BIR domains led to the identification of novel IAP antagonists, and information from co-crystal protein structures was critical in a redesign of the macrocycle that led to antagonists with improved and balanced affinity. The BIR2 and BIR3 binding domains are known to reside in close proximity within the X-linked IAP (XIAP) protein structure. The chapter aims to develop a compound with affinity for both binding sites, and examines the possibility of introducing two binding epitopes into the macrocyclic inhibitors. It further focuses on the design, synthesis and in vivo evaluation of a series of macrocyclic bivalent IAP antagonists with improved potency and pharmacokinetic properties." @default.
• W2765642169 created "2017-11-10" @default.
• W2765642169 creator A5090620847 @default.
• W2765642169 date "2017-08-18" @default.
• W2765642169 modified "2023-10-16" @default.
• W2765642169 title "The Discovery of Macrocyclic IAP Inhibitors for the Treatment of Cancer" @default.
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• W2765642169 doi "https://doi.org/10.1002/9781119092599.ch17" @default.
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