Selisistat (EX 527)

別名：SEN0014196

製品コード：S1541 純度：99.78%

Selisistat (EX 527, SEN0014196) is a potent and selective SIRT1 inhibitor with IC50 of 38 nM in a cell-free assay, exhibits >200-fold selectivity against SIRT2 and SIRT3. Phase 2.

CAS No. 49843-98-3

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 59500	国内在庫あり
100mg	JPY 118500	国内在庫あり
1g	JPY 448500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（277）

製品安全説明書

現在のバッチを見る：純度： 99.78%

99.78

Selisistat (EX 527)関連製品

関連ターゲット	SIRT1 SIRT2 SIRT3 SIRT6 SIRT5	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library FDA-approved Drug Library Natural Product Library Bioactive Compound Library-I Bioactive Compound Library-Ⅱ	もっと見る

シグナル伝達経路

Sirtuinシグナル伝達経路

Sirtuin阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
HUVECs	Apoptosis Assay	10 μM	24 h	bolishes the protective effect of resveratrol in cell viability	23358928
RMECs	Apoptosis Assay	10 μM	24 h	attenuates the anti-apoptotic effect of Des-G	24486147
Platelets	Apoptosis Assay	10/50 μM	10 min	increases ROS level in a dose-dependent manner	25829495
K562	Function Assay	0.1-1 μM	2 h	stimulates Nrf2-dependent gene transcription	21196497
INS-1E	Function Assay	1 μm	24 h	prevents resveratrol-induced up-regulation of Glut2, glucokinase,Pdx-1, and Tfam	21163946
MCF-7	Growth Inhibition Assay	0-100 μM	24/48/72 h	represses cell proliferation at the concentration ≥100 μM	20371709
NCI-H460	Function Assay	1 μm	6 h	produces a concentration-dependent increase in the amount of acetylated p53	16354677
HCT116	Function assay	10 uM	8 hrs	Inhibition of SIRT1 in human HCT116 cells assessed as increase in acetylated p53 at 10 uM after 8 hrs by Western blot analysis	22642300
HeLa	Growth Inhibition Assay		48 h	IC50=8.9 ± 1.9 μM	24998427
HEK 293	Growth Inhibition Assay		48 h	IC50=69.0 ± 0.7 μM	24998427
HeLa	Growth Inhibition Assay		24 h	IC50=37.9 ± 1.8 μM	24998427
HEK 293	Growth Inhibition Assay		24 h	IC50=97.7 ± 8.1 μM	24998427
Namalwa cells	Function assay		3 hrs	Inhibition of SIRT1-mediated endogenous p53 deacetylase activity in human Namalwa cells assessed as concentration required to enhance p53 deacetylation to twice the basal level after 3 hrs by ELISA, INH = 0.6 μM.	25971769
Hs683	Cell cycle assay		24 to 48 hrs	Cell cycle arrest in human Hs683 cells assessed as accumulation at G1 phase at IC50 after 24 to 48 hrs by propidium iodide staining-based flow cytometry	28475330
NCI-H460	Function assay		6 hrs	Inhibition of SIRT-2 in human NCI-H460 cells assessed as inhibition of p53 deacetylation after 6 hrs by immunoprecipitation/immunoblotting analysis, IC50 = 1 μM.	ChEMBL
293T	Function assay			Inhibition of human recombinant GST-tagged SIRT1 expressed in 293T cells by Fluor de Lys fluorescence assay, IC50 = 0.038 μM.	21306906
Escherichia coli cells	Function assay			Inhibition of human recombinant SIRT1 expressed in Escherichia coli cells using acetylated Lys side chain amino acids 379-382 (Arg-His-Lys-Lys(Ac)) p53 conjugated with aminomethylcoumarin as substrate by fluorescence assay, IC50 = 0.16 μM.	22931526
BL21 (DE3)	Function assay			Inhibition of full length human SIRT1 expressed in Escherichia coli BL21 (DE3) cells using fluorogenic 7-amino-4-methylcoumarin (AMC)-labeled peptide by fluorescence assay, IC50 = 0.21 μM.	25275824
BL21 (DE3)	Function assay			Inhibition of full length human SIRT2 expressed in Escherichia coli BL21 (DE3) cells using fluorogenic 7-amino-4-methylcoumarin (AMC)-labeled peptide by fluorescence assay, IC50 = 1.94 μM.	25275824
Escherichia coli cells	Function assay			Inhibition of human recombinant SIRT2 expressed in Escherichia coli cells using acetylated Lys side chain amino acids 379-382 (Arg-His-Lys-Lys(Ac)) p53 conjugated with aminomethylcoumarin as substrate by fluorescence assay, IC50 = 48.5 μM.	22931526
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
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生物活性

製品説明

Selisistat (EX 527, SEN0014196) is a potent and selective SIRT1 inhibitor with IC50 of 38 nM in a cell-free assay, exhibits >200-fold selectivity against SIRT2 and SIRT3. Phase 2.

特性

Greater potency, specificity, stability, and lower toxicity than other inhibitors of SIRT1 catalytic activity identified to date.

Targets

SIRT1 ^[1]
(Cell-free assay)

38 nM

In Vitro
In vitro	EX 527 exhibits potently inhibitory effect against SIRT1 deacetylase activity in a concentration-dependent manner with an IC50 of 38 nM, displays much lower activity against SIRT2 and SIRT3 with IC50 values of 19.6 μM and 48.7 μM, respectively. EX 527 does not inhibit SIRT4-7 and class I/II HDAC activity at concentrations up to 100 μM. EX-527 alone (1 μM) has no detectable effect on the acetylation of p53 lysine 382 in NCI-H460 cells. EX-527 significantly increases the amount of acetylated p53 in NCI-H460 cells, human mammary epithelial cells, U-2 OS and MCF-7 cells subjected to genotoxic agents such as Etoposide, Doxorubicin, Hydroxyurea, and Hydrogen peroxide, which is more effective than that caused by Nicotinamide (5 mM). But surprisingly EX 527 does not result in detectable effects on p53-controled gene expression, cell survival, or cell proliferation. ^[1] EX 527 causes a 90% increase in cell number of HCT116 cells after 7 days in the condition of 0.1% serum but not 10% serum, suggesting that SIRT1 is a significant regulator of cell proliferation during growth factor deprivation conditions. ^[2] EX 527 abrogates resveratrol effects on glucose responses, and prevents resveratrol-induced up-regulation of Glut2, glucokinase, Pdx-1, and Tfam in INS-1E Cells, due to the opposite effect of EX 527 and resveratrol on SIRT1 deacetylase activity. ^[3]
Kinase Assay	Inhibition of GST-SIRT1 deacetylase activity
Kinase Assay	293T cells are transiently transfected with GST-tagged human SIRT1 in the pDEST27 Gateway vector using FuGENE-6. After 48 hours, the cells are lysed with 50 mM Tris, pH 8.0, 120 mM NaCl, 1 mM EDTA, and 0.5% Nonidet P-40, supplemented with Complete Mini protease inhibitor cocktail tablets. GST-SIRT1 is purified from lysates using glutathione-Sepharose beads and washed extensively in the above buffer. The deacetylation assay is performed with approximately 30 ng of GST-SIRT1 in the presence of EX 527 (48 pM to 100 μM). Deacetylation is measured using the Fluor de Lys kit using a fluorogenic peptide encompassing residues 379 to 382 of p53, acetylated on lysine 382. The acetylated lysine residue is coupled to an aminomethylcoumarin moiety. The peptide is deacetylated by SIRT1, followed by the addition of a proteolytic developer that releases the fluorescent aminomethylcoumarin. Briefly, enzyme preparations are incubated with 170 μM NAD⁺ and 100 μM p53 fluorogenic peptide for 45 minutes at 37 °C followed by incubation in developer for 15 minutes at 37 °C. Fluorescence is measured by excitation at 360 nm and emission at 460 nm and enzymatic activity is expressed in relative fluorescence units.
細胞実験	細胞株	NCI-H460, MCF-7, U-2 OS and HMEC
	濃度	Dissolved in DMSO, final concentration 1 μM
	反応時間	48 or 72 hours
	実験の流れ	For viability assays, cells are treated with EX 527 for 48 hours. Cell viability is then determined using the Cell Titer-Glo luminescent assay, which measures total ATP level as an index of cell number. Luminescence is measured on a Luminoskan Ascent. For the proliferation assay, 0.5 μCi/mL of [¹⁴C]thymidine is added to the medium immediately after EX 527. Plates are counted at 48 hours (HMEC) or 72 hours (NCI-H460, MCF-7, and U-2 OS cells) in a Microbeta liquid scintillation counter. Thymidine incorporated by the cells is detected by proximity to the scintillant in the base of the Cytostar-T tissue culture plate.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	GRP78 / FASL / Bcl-2 / LC3 Ac-H3K9 / Fibronectin / Collagen 1 / α-SMA PCNA / Cyclin D1 / Cyclin E pEGFR / EGFR / pPDGFRβ / PDGFRβ pSTAT3 / STAT3 p27 FOXO3a / SIRT1 / Ac-p53 / p16(INK4a)		29312612
	Immunofluorescence	p-p38		26824501
	Growth inhibition assay	Cell viability		24484175

In Vivo
In Vivo	Administration of EX 527 (~10 μg) to rats increases hypothalamic acetyl-p53 levels by inhibiting hypothalamic SIRT1 activity. Co-administration of EX 527 with ghrelin markedly blunts the orexigenic action of ghrelin by decreasing the pAMPK levels, increasing the ACC levels, and abolishing the higher expression of the transcription factors FoxO1, pCREB, and Bsx and the neuropeptides NPY and AgRP in the hypothalamic arcuate nucleus. ^[4]
動物実験	動物モデル	Male Sprague-Dawley rats
	投与量	~5 μg/rat
	投与経路	Intracerebroventricular injection

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT01485965	Completed	Huntington''s Disease	Siena Biotech S.p.A.	November 2011	Phase 1
NCT01521832	Completed	Huntington''s Disease	Siena Biotech S.p.A.	October 2009	Phase 1

参考
[1] Solomon JM, et al. Mol Cell Biol, 2006, 26(1), 28-38. [2] Kabra N, et al. J Biol Chem, 2009, 284(27), 18210-18217. [3] Vetterli L, et al. J Biol Chem, 2011, 286(8), 6049-6060. [4] Velásquez DA, et al. Diabetes, 2011, 60(4), 1177-118 + 展開

参考

[4] Velásquez DA, et al. Diabetes, 2011, 60(4), 1177-118

+ 展開

化学情報

分子量	248.71	化学式	C₁₃H₁₃ClN₂O
CAS No.	49843-98-3	SDF	Download Selisistat (EX 527) SDFをダウンロードする
Smiles	C1CC(C2=C(C1)C3=C(N2)C=CC(=C3)Cl)C(=O)N
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 300 mg/mL ( (1206.22 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 30 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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Handling Instructions

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* 必須

よくある質問（FAQ）

質問1:
what is the extinction coefficient of S1541 WX527?

回答
The extinction coefficient of S1541 EX-527 is 1421.650635.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):