SAR407899 ≥99% 923359-38-0

SAR407899是一种 ATP 竞争型 ROCK 抑制剂，Ki 值为 36 nM（人 ROCK）和 41 nM（大鼠 ROCK）。

Pyronaridine tetraphosphate is an orally active Mannich base anti-malarial agent. Pyronaridine tetraphosphate is active against P. falciparum and Echinococcus granulosus infection

SAR407899 exhibits strong inhibitory action against ROCK by competing with ATP, showing Ki values of 36 nM for human ROCK-2 and 41 nM for rat ROCK-2. It more effectively inhibits ROCK-2 compared to ROCK-1, with inhibition concentrations (IC50s) of 102 ± 19 nM and 276 ± 26 nM, respectively, under conditions of 40 μM ATP. Moreover, SAR407899 inhibits PKC-Δ and MSK-1 with lower potency, having IC50s of 5.4 and 3.1 μM, respectively. In HeLa cells activated by PHEN, SAR407899 at concentrations of 0.1, 0.3, 1.0, and 3.0 μM selectively prevents ROCK-driven phosphorylation of MYPTT696, and demonstrates effectiveness at 1 μM and 10 μM in rat primary aortic smooth muscle cells. A concentration of 3 μM of SAR407899 fully inhibits the contraction of human umbilical vein endothelial cells (HUVECs) triggered by thrombin and formation of stress fibers. It also concentration-dependently reduces 5-bromodeoxyuridine integration into cells with an IC50 of 5.0 ± 1.3 μM and efficiently blocks THP-1 cell migration with an IC50 of 2.5 ± 1.0 μM. SAR407899 shows strong vasorelaxation effects across various isolated arteries from different species and vascular beds, with IC50 values ranging from 122 to 280 nM. Furthermore, SAR407899 relaxes smooth muscle pre-contracted with phenylephrine in a dose-dependent manner, with IC50s of 0.07 and 0.05 μM.