NSC 23766 1177865-17-6

.cp_wz table {border-top: 1px solid #ccc;border-left:1px solid #ccc; } .cp_wz table td{border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;} .cp_wz table th {border-right: 1px solid #ccc;border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;}


Molecular Weight:

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


Biological 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. 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%. 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. 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.


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.


Protocol(Only for Reference)


Kinase Assay: [1]

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 Assay: [5]

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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Baboon	Dog	Monkey	Rabbit	Guinea pig	Rat	Hamster	Mouse
Weight (kg)	12	10	3	1.8	0.4	0.15	0.08	0.02
Body Surface Area (m2)	0.6	0.5	0.24	0.15	0.05	0.025	0.02	0.007
Km factor	20	20	12	12	8	6	5	3

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×	mouse Km(3)	= 11.2 mg/kg
	rat Km(6)

Chemical Information

Molecular Weight (MW)	530.96
Formula	C24H35N7.3HCl
CAS No.	1177865-17-6

Storage	3 years -20℃Powder
	6 months-80℃in solvent (DMSO, water, etc.)
Synonyms

Solubility (25°C) *	In vitro	DMSO	106 mg/mL (199.63 mM)
		Water	106 mg/mL (199.63 mM)
		Ethanol	5 mg/mL (9.41 mM)
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Name	N6-[2-[[4-(Diethylamino)-1-methylbu-tyl]amino]-6-methyl-4-pyrimidinyl]-2-methyl-4,6-qu-inolinediamine trihydrochloride

Molarity Calculator
Dilution Calculator
Molecular Weight Calculator

Contact us if you need more details on 1177865-17-6. We are ready to answer your questions on packaging, logistics, certification or any other aspects about NSC 23766 1177865-17-6、1177865-17-6 NSC 23766. If these products fail to match your need, please contact us and we would like to provide relevant information.

Product Categories : Cell Cycle > Rho Inhibitor