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

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

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 compou...

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Veröffentlicht in:ACS medicinal chemistry letters 2017-03, Vol.8 (3), p.316-320
Hauptverfasser: 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
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Sprache:eng
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Letter
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Zusammenfassung: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.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.6b00481