STO-609 suppresses the functionality of both recombinant CaM-KKα and CaM-KKβ isoforms, exhibiting Ki measurements of 80 and 15 ng/mL for each, respectively, and hampers their self-phosphorylation processes. It demonstrates a pronounced selectivity towards CaM-KK, showing negligible influence on the subsequent CaM kinases (CaM-KI and -IV), with the IC50 against CaM-KII being 10 μg/mL. Both the constitutively active and the wild-type variants of CaM-KKα are inhibited by STO-609. It also curtails the Ca2+-prompted activation of CaM-KIV within HeLa cells that have undergone transfection, operating in a concentration-dependent fashion. Moreover, at a dose of 1μg/mL, STO-609 markedly lowers the inherent activity of CaM-KK in SH-SY5Y neuroblastoma cells, achieving an inhibition rate of 80% [1].
体外研究
STO-609 suppresses the functionality of both recombinant CaM-KKα and CaM-KKβ isoforms, exhibiting Ki measurements of 80 and 15 ng/mL for each, respectively, and hampers their self-phosphorylation processes. It demonstrates a pronounced selectivity towards CaM-KK, showing negligible influence on the subsequent CaM kinases (CaM-KI and -IV), with the IC50 against CaM-KII being 10 μg/mL. Both the constitutively active and the wild-type variants of CaM-KKα are inhibited by STO-609. It also curtails the Ca2+-prompted activation of CaM-KIV within HeLa cells that have undergone transfection, operating in a concentration-dependent fashion. Moreover, at a dose of 1μg/mL, STO-609 markedly lowers the inherent activity of CaM-KK in SH-SY5Y neuroblastoma cells, achieving an inhibition rate of 80% [1].
作用机制
STO-609 permeates cells and competes with ATP to bind to the ATP-binding pocket on CaM-KK, thereby preventing them from activating the phosphorylation of CaM kinases.
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