Rational Design of Apoptosis Signal-Regulating Kinase 1 Inhibitors: Discovering Novel Structural Scaffold
     
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Rational Design of Apoptosis Signal-Regulating Kinase 1 Inhibitors: Discovering Novel Structural Scaffold

New publication: Rational Design of Apoptosis Signal-Regulating Kinase 1 Inhibitors: Discovering Novel Structural Scaffold

 

OTAVAchemicals manuscript on new ASK1 inhibitors has been published in European Journal of Medicinal Chemistry

Abstract: Increased activity of apoptosis signal-regulating kinase 1 (ASK1) is associated with a number of human disorders and the inhibitors of ASK1 may become important compounds for pharmaceutical application. Here we report novel ASK1 inhibitor scaffold, namely 5-(5-Phenyl-furan-2-ylmethylene)-2-thioxo-thiazolidin-4-one, that has been identified using virtual screening and biochemical tests.

A series of derivatives has been synthesized and evaluated in vitro towards human protein kinase ASK1. It was revealed that the most active compounds 4-((5Z)-5-{[5-(4-bromophenyl)-2-furyl]methylene}-4-oxo-2-thioxo-1,3-thiazolidin-3-yl)butanoic acid and 6-((5Z)-5-{[5-(4-bromophenyl)-2-furyl]methylene}-4-oxo-2-thioxo-1,3-thiazolidin-3-yl)hexanoic acid inhibit ASK1 with IC50 of 0.2 µM. Structure-activity relationships of 30 derivatives of 5-(5-Phenyl-furan-2-ylmethylene)-2-thioxo-thiazolidin-4-one have been studied and binding mode of this chemical class has been predicted.

PMID: 23041041

 
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