Z62954982

Z62954982 (ZINC08010136) is a potent, selective and?cell-permeable Rac1 (IC₅₀=12 μM) inhibitor that is 4 times more effective than NSC23766 (HY-15723A) (IC₅₀=50 μM). Z62954982?disrupts the Rac1/Tiam1 complex and decreases cytoplasmic levels of active Rac1 (GTP-bound Rac1), without affecting the activity of other Rho GTPases (such as Cdc42 or RhoA)^[1][2]. In Vitro: Z62954982 (5-100 μM; 4 hours) reduces the intracellular levels of Rac1- GTP in a concentration-dependent manner,and shows the most potent inhibitory action with an IC₅₀ of 12.2 μM in Human SMCs^[1].
Z62954982 (25 μM; 4 hours) significantly reduces the ratio Rac1-GTP/Rac1 and has the most potent inhibitory action (86.0%) in cultured SMCs^[1].
Z62954982 (10-100 μM; 72 hours) causes a concentration-dependent decrease in transendothelial electrical resistance (TER) in both HDMEC and HUVEC monolayers^[2].
In Vivo: Z62954982 (intraperitoneal?injection; 10 mg/kg every other day or 20 mg/kg daily; 3 weeks) has no obvious signs of toxicity and decreases both phosphorylation of p38 as well as secreted IL-6 in PASMCs in response to hypoxia in both abr^-/- and?bcr^-/- mice^[3].