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Design, Synthesis, and Biological Evaluation of Imidazopyrazinone Derivatives as Antagonists of Inhibitor of Apoptosis Proteins (IAPs)
Author(s) -
Kim Jisook,
Bae Inhwan,
Song Jiyoung,
Kim Younghoon,
Ahn Younggil,
Park HyunJu,
Kim Ha Hyung,
Kim Dae Kyong
Publication year - 2021
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.12271
Subject(s) - apoptosis , antagonist , inhibitor of apoptosis , chemistry , potency , pharmacology , cancer research , caspase , cell growth , recombinant dna , microbiology and biotechnology , in vitro , biochemistry , receptor , programmed cell death , biology , gene
Apoptosis inhibitor (IAP) proteins are overexpressed in many cancers and implicated in tumor growth, so the development of antagonist that disrupts with the binding of IAP to their partner protein is a promising therapeutic strategy. In an effort to increase cellular activity and improve favorable drug‐like properties, we newly designed and synthesized monovalent analogues based on imidazopyrazinone structure of 9 . Optimization of cellular potency led to the identification of 17 , which showed increase of submicromolar activity (GI 50 = 234 nM) and caspase‐3 activation (6.3‐fold) in MDA‐MB‐231 breast cancer cells. These findings clearly show the potential for 17 as a promising monovalent antagonist for the development of an effective anticancer treatment.