Structure-Based Design of ASK1 Inhibitors as Potential Agents for Heart Failure.

ACS Med Chem Lett

Departments of Medicinal Chemistry, Drug Metabolism Pharmacokinetics, Structural Biology, and Discovery Biology, Gastrointestinal Drug Discovery Unit, Takeda Pharmaceuticals , 10410 Science Center Drive, San Diego, California 92121, United States.

Published: March 2017

Apoptosis signal-regulating kinase 1 (ASK1/MAP3K) is a mitogen-activated protein kinase family member shown to contribute to acute ischemia/reperfusion injury. Using structure-based drug design, deconstruction, and reoptimization of a known ASK1 inhibitor, a lead compound was identified. This compound displayed robust MAP3K pathway inhibition and reduction of infarct size in an isolated perfused heart model of cardiac injury.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346976PMC
http://dx.doi.org/10.1021/acsmedchemlett.6b00481DOI Listing

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