NSC 23766 trihydrochloride

• CAT Number: I000633
• CAS Number: 1177865-17-6
• Molecular Formula: C24H35N7 • 3HCl
• Molecular Weight: 531
• Purity: ≥95%
• Target: Rho
• Solubility: DMSO: ≤ 7.6 mg/mL
• Storage: 3 years -20C powder
• IC50: 50 uM
• InChIKey: DEFBCZWQLILOJF-UHFFFAOYSA-N

NSC 23766 3Hcl is a specific inhibitor of the binding and activation of RAC GTPase with IC50 of ~50 μM; does not inhibit the closely related targets, Cdc42 or RhoA.IC50 value: 50 uMTarget: RAC GTPasein vitro: NSC23766 is identified to fit into a surface groove of Rac1 known to be critical for GEF specification. NSC23766 effectively inhibits Rac1 binding and activation by the Rac-specific GEF Trio or Tiam1 in a dose-dependent manner without interfering with the closely related Cdc42 or RhoA binding or activation by their respective GEFs or with Rac1 interaction with BcrGAP or effector PAK1 [1]. 50 μM NSC 23766 inhibits thrombin-induced activation of Rac1 an d Rac2 in human platelets, as well as platelet aggregation [2]. NSC23766 regulates endothelial nitric oxide synthase expression and endothelial function. 100 μM NSC23766 represses the eNOS promoter activity by 60% in bovine aortic ECs and by 30% to 35% in bEND.3 cells. Inhibition of Rac1 with NSC23766 destabilizes eNOS mRNA and shortens its half-life to 17 hours. NSC23766 dose-dependently attenuates ACh-induced relaxation of wild-type mice aortic rings [3].in vivo: NSC23766 induces mobilization of hematopoietic stem cells/progenitors. Intraperitoneal administration of NSC23766 (2.5 mg/kg) into the ‘‘poorly mobilizing ’’ C57Bl/6 mouse strain leads to a two-fold increase in circulating hematopoietic stem cells progenitors 6 hr after injection [2]. NSC23766 alleviates lipopolysaccharide-induced acute pulmonary injury in mice. Treatment with NSC23766 at 1 or 3mg/kg not only reduces the inflammatory cells infiltration and MPO activities, but also inhibits pro-inflammatory mediators, tumor necrosis factor-α and interleukin-1β, mRNA expression. NSC23766 also reduces Evans Blue and albumin accumulation in LPS-challenged lungs [4].

Reference

[1]. Gao Y, et al. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci U S A, 2004, 101(20), 7618-7623.
[2]. Akbar H, et al. Rational design and applications of a Rac GTPase-specific small molecule inhibitor. Methods Enzymol, 2006, 406, 554-565.
[3]. Sawada N, et al. Regulation of endothelial nitric oxide synthase and postnatal angiogenesis by Rac1. Circ Res, 2008, 103(4), 360-368.
[4]. Yao HY, et al. Inhibition of Rac activity alleviates lipopolysaccharide-induced acute pulmonary injury in mice. Biochim Biophys Acta, 2011, 1810(7):666-674.