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

Publication Type:

Journal Article

Authors:

Lanier, Marion; Pickens, Jason; Bigi, Simone V; Bradshaw-Pierce, Erica L; Chambers, Alison; Cheruvallath, Zacharia S; Cole, Derek; Dougan, Douglas R; Ermolieff, Jacques; Gibson, Tony; Halkowycz, Petro; Hirokawa, Aki; Ivetac, Anthony; Miura, Joanne; Nunez, Evan; Sabat, Mark; Tyhonas, John; Wang, Haixia; Wang, Xiaolun; Swann, Steve

Source:

ACS Med Chem Lett, Volume 8, Issue 3, p.316-320 (2017)

Abstract:

<p>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.</p>

PDB: 
5UP3, 5UOR, 5UOX for ASK1_1, ASK1_6, ASK1_17, and ASK1_19 respectively
Detector: 
PILATUS
Beamline: 
24-ID-C