NSC 23766 trihydrochloride

製品コードS8031 バッチS803102

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₄H₃₅N₇.3ClH
	分子量	530.97	CAS No.	1177865-17-6
Solubility (25°C)*	体外	DMSO	100 mg/mL warmed with 50ºC water bath (188.33 mM)
		Water	100 mg/mL warmed with 50ºC water bath (188.33 mM)
		Ethanol	Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
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]
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]

製品説明

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.

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]

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]

プロトコル(参考用のみ)

キナーゼアッセイ	Rho GTPase activity assay
キナーゼアッセイ	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.
細胞アッセイ	細胞株	Human breast cancer cells MDA-MB-468
	濃度	0-100 μM
	反応時間	2 days
	実験の流れ	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.
動物実験	動物モデル	Male ICR mic
	投薬量	1 or 3 mg/kg
	投与方法	i.p.

参考

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カスタマーフィードバック

: Data from [Data independently produced by , , Science, 2018, 11(528), doi: 10.1126/scisignal.aao6897]

: Data from [Data independently produced by , , Cell Death Dis, 2015, 6: e1751 ]

: Data from [Data independently produced by , , J Immunol, 2017, 198(4):1696-1705]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Sema3C signaling is an alternative activator of the canonical WNT pathway in glioblastoma [ Nat Commun, 2023, 14(1):2262]	PubMed: 37080989
SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion [ Exp Mol Med, 2023, 55(4):779-793]	PubMed: 37009792
DEF6-differentially exprehomolog) exacerbates pathological cardiac hypertrophy via RAC1 [ Cell Death Dis, 2023, 10.1002/1878-0261.13537]	PubMed: 37524688
Knockdown of Porf-2 restores visual function after optic nerve crush injury [ Cell Death Dis, 2023, 14(8):570]	PubMed: 37640747
TIAM1 acts as an actin organization regulator to control adipose tissue-derived pericyte cell fate [ JCI Insight, 2023, 8(13)e159141]	PubMed: 37219951
Hydrogel viscoelasticity modulates migration and fusion of mesenchymal stem cell spheroids [ Bioeng Transl Med, 2023, 8(3):e10464]	PubMed: 37206235
Regulation of De Novo Lipid Synthesis by the Small GTPase Rac1 in the Adipogenic Differentiation of Progenitor Cells from Mouse White Adipose Tissue [ Int J Mol Sci, 2023, 24(5)4608]	PubMed: 36902044
Regulation of De Novo Lipid Synthesis by the Small GTPase Rac1 in the Adipogenic Differentiation of Progenitor Cells from Mouse White Adipose Tissue [ Int J Mol Sci, 2023, 24(5)4608]	PubMed: 36902044
Rac1/PAK1 signaling contributes to bone cancer pain by Regulation dendritic spine remodeling in rats [ Mol Pain, 2023, 19:17448069231161031]	PubMed: 36938611
Hedgehog signaling is controlled by Rac1 activity [ Theranostics, 2022, 12(3):1303-1320]	PubMed: 35154488

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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