2. Academic Validation
  3. Structure-Based Design of ASK1 Inhibitors as Potential Agents for Heart Failure

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

  • ACS Med Chem Lett. 2017 Feb 8;8(3):316-320. doi: 10.1021/acsmedchemlett.6b00481.
Marion Lanier 1,  Jason Pickens 1,  Simone V Bigi 1,  Erica L Bradshaw-Pierce 1,  Alison Chambers 1,  Zacharia S Cheruvallath 1,  Derek Cole 1,  Douglas R Dougan 1,  Jacques Ermolieff 1,  Tony Gibson 1,  Petro Halkowycz 1,  Aki Hirokawa 1,  Anthony Ivetac 1,  Joanne Miura 1,  Evan Nunez 1,  Mark Sabat 1,  John Tyhonas 1,  Haixia Wang 1,  Xiaolun Wang 1,  Steve Swann 1
Affiliations

Affiliation

  • 1 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.
PMID: 28337323 DOI: 10.1021/acsmedchemlett.6b00481
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.

Keywords

Apoptosis signal-regulating kinase 1 (ASK1); cardiac injury; structure-based drug design (SBDD).

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