product name NSC 23766
Description: NSC 23766 is a potent inhibitor of Rac GTPase targeting Rac activation by guanine nucleotide exchange factors (GEFs) with IC50 of ~50 μM in a cell-free assay; it does not inhibit the closely related targets, Cdc42 or RhoA. NSC23766 disrupted polar secretion of adhesive, polarization of endomembranes, and tip-focused growth in the rhizoid. NSC23766 can acts as a competitive antagonist at muscarinic acetylcholine receptors. NSC23766 exerts anti-influenza virus properties by affecting the viral polymerase complex activity. NSC23766 suppresses CREB signaling by targeting NMDA receptor function.
References: Proc Natl Acad Sci U S A. 2004 May 18;101(20):7618-23; Methods Enzymol. 2006;406:554-65.
421.58
Formula
C24H35N7
CAS No.
733767-34-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 10 mM
Water:
Ethanol:
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: 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. 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. Kinase Assay: Cell Assay: In human dermal microvascular endothelial cells, NSC-23766 decreased trans-endothelial electrical resistance and caused the intercellular gap formation. Inhibition of Rac 1 by NSC-23766 shortly reduced endothelial barrier functions as revealed by measurement of TER and the appearance of intracellular gaps. In the mucous cell of the intestine, inhibition of Rac1 either by NSC-23766 protected cells from TNF-α-induced apoptosis by inhibiting caspase-3, -8 and -9 activities. Inhibition of Rac1 significantly prevented TNF-α-induced activation of JNK1/2, but did not modulate TNF-α-induced ERK1/2, Akt and p38 MAPK activity. |
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| 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. 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. |
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| Formulation & Dosage | |
| References | Proc Natl Acad Sci U S A. 2004 May 18;101(20):7618-23; Methods Enzymol. 2006;406:554-65. |
