1090893-12-1

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].

A cell-permeable isoxazolyl-benzamide compound that is more effective than NSC23766 (Cat. Nos. 553502 & 553508) in inhibiting PDGF-BB- (Cat. No. 521225) induced cellular Rac1 activation (45.8% vs 11.1% inhibition by 4 h pretreatment of the respective compound at 50 μM) in serum-starved SMCs (human aortic smooth muscle cells) by interfering Rac1-Tiam1 interaction, while exhibiting no effect toward cellular Cdc42 and RhoA activation or Rac1 interaction to its effector Pak1. Shown to effectively prevent PDGF-BB-induced membrane ruffling and lamellipodia formation in serum-starved 3T3 cells (4 h pretreatment at 25 μM). Also available in InSolution format (Cat. No. 553512).

[1] Nicola Ferri,et al. Virtual Screening Approach for the Identification of New Rac1 Inhibitors. J Med Chem. 2009 Jul 23;52(14):4087-90. DOI:10.1021/jm8015987
[2] Xun E Zhang, et al. Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement. PLoS One. 2016 May 17;11(5):e0155490. DOI:10.1371/journal.pone.0155490
[3] Min Yu, et al. Lack of BCR and Abr Promotes Hypoxia-Induced Pulmonary Hypertension in Mice. PLoS One DOI:10.1371/journal.pone.0049756