NSC 23766 trihydrochloride

SKU: orb1300851

Description

NSC 23766 trihydrochloride is a cell-permeable inhibitor that selectively blocks Rac1 GTPase activation by guanine nucleotide exchange factors (GEFs) with an IC50 of approximately 50 μM. It exhibits high specificity for Rac1 over the related Rho GTPases RhoA and Cdc42. This inhibitor is widely used in vitro to study Rac1-mediated cellular processes such as cytoskeletal reorganization, cell migration, and NADPH oxidase activation.

Research Area

Cell Biology, Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 1177865-17-6
• MW: 530.96
• Purity: 99.75% (May vary between batches)
• Formula: C₂₄H₃₅N₇·3HCl
• SMILES: Cl.Cl.Cl.CCN(CC)CCCC(C)Nc1nc(C)cc(Nc2ccc3nc(C)cc(N)c3c2)n1
• Target: Apoptosis,Rho,Ras
• Solubility: DMSO:53.1 mg/mL (100.01 mM);H2O:53.1 mg/mL (100.01 mM)

Bioactivity

• Target IC50:
  Rac GTPase:50 μM
• 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 3 mg/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.
• In 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. NSC 23766 is active in regulating Rac GTPase functions on cytoskeleton and many cell functions including cell cycle, cell growth, adhesion, migration and gene transcription. NSC 23766 (50 μM) potently blocks serum or platelet-derived growth factor-induced Rac1 activation and lamellipodia formation without affecting the activity of endogenous Cdc42 or RhoA in NIH 3T3 cells. NSC 23766 reduces Trio or Tiam1 but not Vav, Lbc, Intersectin, or a constitutively active Rac1 mutant-stimulated NIH 3T3 cells growth and suppresses Trio, Tiam1, or Ras-induced cell transformation. NSC23766 dose-dependently inhibits PC-3 cells proliferation and anchorage-independent growth. 25 μM NSC23766 inhibits the PC-3 cell invasion through Matrigel by 85%. 50 μM NSC 23766 inhibits thrombin-induced activation of Rac1 an d Rac2 in human platelets, as well as platelet aggregation. NSC23766 prevents Aβ40 and Aβ42 production in swAPP-HEK293cells without affecting Notch and sAPPα. NSC23766 prevents γ-secretase activity in cell, but not act as a direct γ-secretase inhibitor. NSC23766 dose-dependently reduces levels of secreted and intracellular Aβ40 with IC50 of 48.94 μM. 50 μM NSC 23766 inhibits release of Aβ42 by 57.97%.
• Cell Research:
  Cells (1.5 × 104/mL) are seeded in each well of 96-well tissue culture plates with 200 μL of medium. After 24 hours of plating, the medium is replaced with 200 μL of fresh medium containing NSC23766 at the indicated concentrations. At the end of the treatment period 20 μL of MTS solution are added to each well and incubated at 37 ℃ for 2 hours. Absorbance at 490 nm is read on a 96-well plate reader.(Only for Reference)

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Rac GTPase, Ras, Apoptosis, NSC23766, NSC-23766, NSC23766 Trihydrochloride, NSC-23766 Trihydrochloride

Compound Identifiers

PubChem CID

16759159