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NSC 23766 trihydrochloride

NSC 23766 trihydrochloride is an inhibitor of Rac GTPase targeting Rac activation by guanine nucleotide exchange factors (GEFs) with IC50 of ~50 μM in a cell-free assay; does not inhibit the closely related targets, Cdc42 or RhoA.

NSC 23766 trihydrochloride Chemical Structure

NSC 23766 trihydrochloride Chemical Structure

CAS No. 1177865-17-6

Purity & Quality Control

NSC 23766 trihydrochloride Related Products

Signaling Pathway

Rho Signaling Pathways

Rho Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
RA4 Function Assay 50 μM 24 h inhibits Matrigel invasion 17622308
RA3 Function Assay 50 μM 24 h inhibits Matrigel invasion 17622308
RA2 Function Assay 50 μM 24 h inhibits Matrigel invasion 17622308
RA1 Function Assay 50 μM 24 h inhibits Matrigel invasion 17622308
RA-FLS (RA2)  Growth Inhibition Assay 25/50 μM 1-9 d inhibits cell growth in both dose and time dependent manner 17622308
IEC-6  Function Assay 120 µM 4/6/8 h prevents the increased activation of FAK at 6 and 8 h 20448461
MDA-MB-231  Function Assay 50/100 μM 48 h induces a dose-dependent decrease in phosphorylation of p65 subunit 20515940
MDA-MB-468 Function Assay 50/100 μM 48 h induces a dose-dependent decrease in phosphorylation of p65 subunit 20515940
MDA-MB-231  Function Assay 50/100 μM 24 h increases phosphorylation of JNK in a dose dependent manner 20515940
MDA-MB-468 Function Assay 50/100 μM 24 h increases phosphorylation of JNK in a dose dependent manner 20515940
MDA-MB-468 Function Assay 100 μM 24 h inhibits caspase-3 activation  20515940
MDA-MB-468 Apoptosis Assay 50/100 μM 24 h induces apoptosis 20515940
T47D Function Assay 100 μM 48 h increases the cell number in G1 phase and decreases the cell number in S and G2-M phases  20515940
MCF7 Function Assay 100 μM 48 h increases the cell number in G1 phase and decreases the cell number in S and G2-M phases  20515940
MDA-MB-231  Function Assay 100 μM 48 h increases the cell number in G1 phase and decreases the cell number in S and G2-M phases  20515940
MDA-MB-231 Function Assay 0-100 μM 24 h selectively inhibits Rac1 activation without interfering with the activity of the closely related small GTPase Cdc42 20515940
MDA-MB-231 Cytotoxicity Assay 0-100 μM 48 h decreases cell viability in a dose dependent manner 20515940
MDA-MB-468 Cytotoxicity Assay 0-100 μM 48 h decreases cell viability in a dose dependent manner 20515940
T47D Cytotoxicity Assay 0-100 μM 48 h decreases cell viability in a dose dependent manner 20515940
MCF7 Cytotoxicity Assay 0-100 μM 48 h decreases cell viability in a dose dependent manner 20515940
SKBR3-pMKO.1 Function Assay 50 μM 24 h inhibits Rac1 activation 21943825
SKBR3 Function Assay 50 μM 24 h inhibits Rac1 activation 21943825
NCI-H1703 Function Assay 0-500 μM 24 h diminishes basal NF-κB activity dose dependently  22549160
NCI-H1703 Function Assay 100 μg/ml 24 h slows progression through the G1 phase of the cell cycle 22549160
NCI-H1703 Growth Inhibition Assay 0-500 μM 24 h inhibits cell growth in a dose dependent manner 22549160
T98MG Function Assay 50 mM 24 h DMSO enhances the antimigratory effect of erlotinib 23832120
A172MG Function Assay 50 mM 24 h DMSO enhances the antimigratory effect of erlotinib 23832120
U87MG Function Assay 50 mM 24 h DMSO enhances the antimigratory effect of erlotinib 23832120
PC40 Cell Viability Assay 50 mM 144 h DMSO exhibits synergistic antiproliferative effects combined treatment with erlotinib  23832120
PC38 Cell Viability Assay 50 mM 144 h DMSO exhibits synergistic antiproliferative effects combined treatment with erlotinib  23832120
T98MG Cell Viability Assay 50 mM 144 h DMSO exhibits synergistic antiproliferative effects combined treatment with erlotinib  23832120
A172MG Cell Viability Assay 50 mM 144 h DMSO exhibits synergistic antiproliferative effects combined treatment with erlotinib  23832120
U87MG Cell Viability Assay 50 mM 144 h DMSO exhibits synergistic antiproliferative effects combined treatment with erlotinib  23832120
Ki-67+ CLL Growth Inhibition Assay 50 µM 5 d decreases the number of Ki-67+ CLL cells 24501217
NIH3T3  Growth Inhibition Assay 100 μM 24 h has no significant impact on cell viability 25037060
U2-OS Function Assay 100 μM 24 h DMSO induces cell cycle arrest in the G1 phase  25109327
SW480  Function Assay 100 μM 24 h DMSO induces cell cycle arrest in the G1 phase  25109327
A431 Function Assay 100 μM 24 h DMSO induces cell cycle arrest in the G1 phase  25109327
U2-OS Growth Inhibition Assay 100 μM 24/48/72 h inhibits cell growth in a time dependent manner 25109327
SW480  Growth Inhibition Assay 100 μM 24/48/72 h inhibits cell growth in a time dependent manner 25109327
A431 Growth Inhibition Assay 100 μM 24/48/72 h inhibits cell growth in a time dependent manner 25109327
RBMECs Function Assay 100 μM  30 min blockes 6Bnz-cAMP-mediated activation of Rac1 in EMAP-II-treated RBMECs 26358039
human aortic smooth muscle cells Function Assay 50 uM Inhibition of Rac1 binding to Pak1 in human aortic smooth muscle cells at 50 uM by SDS-PAGE based chemiluminescence 19527032
human aortic smooth muscle cells Function Assay 100 μM Inhibition of Rac1 binding to Pak1 in human aortic smooth muscle cells at 100 uM by SDS-PAGE based chemiluminescence 19527032
Click to View More Cell Line Experimental Data

Biological Activity

Description NSC 23766 trihydrochloride is an inhibitor of Rac GTPase targeting Rac activation by guanine nucleotide exchange factors (GEFs) with IC50 of ~50 μM in a cell-free assay; does not inhibit the closely related targets, Cdc42 or RhoA.
Targets
Rac GTPase [1]
(Cell-free assay)
50 μM
In vitro
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. [1]

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%. [1] 50 μM NSC 23766 inhibits thrombin-induced activation of Rac1 an d Rac2 in human platelets, as well as platelet aggregation. [2]

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%. [3]

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. [4]

NSC23766 inhibits cell growth and induces apoptosis. NSC23766 decreases MDA-MB-468 and MDA-MB-231 cells viability in a dose-dependent manner with IC50 of ~10 μM, which is not correlated with the status of estrogen receptor (ER), progesterone receptor (PR), Her2, and p53 mutation. NSC23766 has little effect on the survival of the MCF12A normal mammary epithelial cells. After 24 hours expose to NSC 23766, MDA-MB-231 cells showes an increase from 41% to 65% in G1 phase and a concomitant decrease in S and G2-M phases. 100 μM NSC23766 induces a six-fold increase of apoptotic MDA-MB-468. The inhibition of NSC23766 on cell cycle arrest or apoptosis in breast cancer cells is mediated by downregulation of cyclin D1, survivin, and X-linked inhibitor of protein apoptosis. [5]
Kinase Assay Rho GTPase activity assay
Cells are grown in log phase in a 10-cm dish, and are starved in 0.5% serum medium or indicated otherwise for 24 h before lysis in a buffer containing 20 mM Tris HCl (pH 7.6), 100 mM NaCl, 10 mM MgCl2, 1% Nonidet P-40, 10% glycerol, and 1× protease inhibitor mixture. Lysates are clarified, the protein concentrations are normalized, and the GTP-bound Rac1 in the lysates is measured by an effector domain pull-down assay. For the His6-PAK1 PBD pull-down assay, cell lysates are incubated with Ni2+-agarose-immobilized His6-PAK1 PBD domain (∼1 μg each) purified from E. coli for 30 min. The Ni2+-agarose co-precipitates are washed twice in the wash buffer and analyzed by immunoblotting with anti-Rac1 monoclonal antibody.
Cell Research Cell lines Human breast cancer cells MDA-MB-468
Concentrations 0-100 μM
Incubation Time 2 days
Method

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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot active Rac1 / Rac1 OCT4 / SOX2 / Nanog pCREB / CREB 31338333
Immunofluorescence BART / Rac1 IP3K-A / F-actin 22745590
In Vivo
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. [6]
Animal Research Animal Models Male ICR mic
Dosages 1 or 3 mg/kg
Administration i.p.

Chemical Information & Solubility

Molecular Weight 530.97 Formula

C24H35N7.3ClH
CAS No. 1177865-17-6 SDF Download NSC 23766 trihydrochloride SDF
Smiles CCN(CC)CCCC(C)NC1=NC(=CC(=N1)NC2=CC3=C(C=C(N=C3C=C2)C)N)C.Cl.Cl.Cl
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 106 mg/mL ( (199.63 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 106 mg/mL

Ethanol : 5 mg/mL


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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