产品描述:
SAR407899 is an ATP-competitive inhibitor of the Rho-associated kinases ROCK1 and ROCK2 (IC50s = 102 and 276 nM, respectively at a concentration of 40 μM ATP).{37269} SAR407899 is selective for ROCK over 79 other kinases at IC50 values up to 10 μM but had IC50 values ranging from 1 to 10 μM for RSK, PKB, PKCδ, and MSK-1. It is also selective for ROCK over 115 receptor and enzyme targets at IC50 values up to 10 μM, but it does inhibit the serotonin transporter and µ-opioid receptors with IC50 values of 1.1 and 8.9 μM, respectively. In vitro, SAR407899 inhibits ROCK-mediated phosphorylation of myosin phosphatase (MYPT), thrombin-induced stress fiber formation, PDGF-induced proliferation, and monocyte chemotactic protein-1-stimulated chemotaxis. SAR407899 relaxes precontracted isolated arteries from various species (IC50s = 122-280 nM) and precontracted corpora cavernosa in both healthy and diabetic animals (IC50s = 0.05-0.42 μM).{37269},{37270} It inhibits constriction of rat and human arteries induced by endothelin-1 (ET-1; Emaxs = 24-83% of control).{37271}