SR-318 is a potent and selective type-II inhibitor that targets p38α/β in an inactive DFG-out conformation with good kinome selectivity (p38α/β IC50 = 5/39 nM by radiometric kinase assay). SR-318 selectively inhibits p38α/β by cell-based NanoBRET assay (IC50 = 3.7 nM/p38α, 10 nM/p38β, 0.91 μM/ZAK, ≥3 μM/DDR1, DDR2, KIT, MYLK4, RSK4) and effectively blocks LPS-induced TNF-α release in human whole blood (IC50 = 283 nM). SR-321 is an inactive structural analog and the recommended negative control compound.
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Journal of medicinal chemistry, 62(23), 10757-10782 (2019-11-09)
p38 mitogen-activated protein kinases are key mediators of environmental stress response and are promising targets for treatment of inflammatory diseases and cancer. Numerous efforts have led to the discovery of several potent inhibitors; however, so far no highly selective type-II
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