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

ABSTRACT: 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.

SUBMITTER: Lanier M

PROVIDER: S-EPMC5346976 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Lanier Marion M Pickens Jason J Bigi Simone V SV Bradshaw-Pierce Erica L EL Chambers Alison A Cheruvallath Zacharia S ZS Cole Derek D Dougan Douglas R DR Ermolieff Jacques J Gibson Tony T Halkowycz Petro P Hirokawa Aki A Ivetac Anthony A Miura Joanne J Nunez Evan E Sabat Mark M Tyhonas John J Wang Haixia H Wang Xiaolun X Swann Steve S

ACS medicinal chemistry letters 20170208 3

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. ...[more]

PMID: 28337323

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