Marion Lanier, Jason Pickens, Simone V Bigi, Erica L Bradshaw-Pierce, Alison Chambers, Zacharia S Cheruvallath, Derek Cole, Douglas R Dougan, Jacques Ermolieff, Tony Gibson, Petro Halkowycz, Aki Hirokawa, Anthony Ivetac, Joanne Miura, Evan Nunez, Mark Sabat, John Tyhonas, Haixia Wang, Xiaolun Wang, Steve Swann
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.
March 9, 2017: ACS Medicinal Chemistry Letters