Biochem/physiol Actions

HS38 is a potent and selective ATP-competitive inhibitor of Death-associated protein kinases DAPK1 (IC₅₀ = 200 nM, 89% inhibition at 10 RM) and ZIPK (Zipper-interacting protein kinase, also called DAPK3) that regulate programmed cell death, and also inhibits the closely related PIM3 kinase (IC₅₀ = 200 nM, 76% inhibition at 10 RM). In addition to mediating apoptosis, DAPK1 and ZIPK regulate both non-muscle and smooth muscle myosin phosphorylation. HS38 specifically targeted ZIPK in smooth muscle, and decreased contractile force generated in mouse aorta, rabbit ileum, and calyculin A stimulated arterial muscle.