Selisistat (EX 527)

製品コードS1541 バッチS154106

印刷

化学情報

Synonyms

SEN0014196

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₃H₁₃ClN₂O

分子量

248.71

CAS No.

49843-98-3

Solubility (25°C)*

体外

DMSO

35 mg/mL (140.72 mM)

Ethanol

20 mg/mL (80.41 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	3.000mg/ml (12.06mM)	Taking the 1 mL working solution as an example, add 50 μL of 60 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	3.000mg/ml (12.06mM)	Taking the 1 mL working solution as an example, add 50 μL of 60 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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	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.
in vitro	Selisistat (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. It does not inhibit SIRT4-7 and class I/II HDAC activity at concentrations up to 100 μM. This compound alone (1 μM) has no detectable effect on the acetylation of p53 lysine 382 in NCI-H460 cells, but 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 Hydrogen peroxide, which is more effective than that caused by Nicotinamide (5 mM). Surprisingly, it does not result in detectable effects on p53-controled gene expression, cell survival, or cell proliferation. ^[1] It 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] The compound 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]
in vivo	Administration of Selisistat (EX 527) (~10 μg) to rats increases hypothalamic acetyl-p53 levels by inhibiting hypothalamic SIRT1 activity. Co-administration of this compound 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]
特徴	Greater potency, specificity, stability, and lower toxicity than other inhibitors of SIRT1 catalytic activity identified to date.

プロトコル(参考用のみ)

キナーゼアッセイ	Inhibition of GST-SIRT1 deacetylase activity
キナーゼアッセイ	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 and washed extensively in the above buffer. The deacetylation assay is performed with approximately 30 ng of GST-SIRT1 in the presence of Selisistat (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.
細胞アッセイ	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 Selisistat (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 this compound. 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.
動物実験	動物モデル	Male Sprague-Dawley rats
	投薬量	~5 μg/rat
	投与方法	Intracerebroventricular injection

参考

https://pubmed.ncbi.nlm.nih.gov/16354677/
https://pubmed.ncbi.nlm.nih.gov/19433578/
https://pubmed.ncbi.nlm.nih.gov/21163946/

https://pubmed.ncbi.nlm.nih.gov/21386086/

+ 展开

カスタマーフィードバック

: Data from [Data independently produced by J Pineal Res, 2014, 57(2), 228-38]

: Data from [Cancer Res, 2014, 74(1), 298-308]

: Data from [Data independently produced by J Trauma Acute Care Surg, 2014, 10.1097/TA.0347]

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：

Ethyl Lactate Ameliorates Hepatic Steatosis and Acute-on-Chronic Liver Injury in Alcohol-Associated Liver Disease by Inducing Fibroblast Growth Factor 21 [ Adv Sci (Weinh), 2025, 12(5):e2409516]	PubMed: 39661730
(+)-JQ-1 alleviates cardiac injury in myocardial infarction by inhibiting ferroptosis through the NAMPT/SIRT1 pathway [ Cell Death Dis, 2025, 16(1):548]	PubMed: 40695797
IDH1 regulates human erythropoiesis by eliciting chromatin state reprogramming [ Elife, 2025, 13RP100406]	PubMed: 40299922
Human umbilical cord mesenchymal stem cell-derived exosomes repair IBD by activating the SIRT1-FXR pathway in macrophages [ Stem Cell Res Ther, 2025, 16(1):233]	PubMed: 40346712
SIRT1 and its SUMOylation attenuate hyperoxia-induced lung injury by improving mitochondrial biogenesis and fusion [ Free Radic Biol Med, 2025, 236:98-115]	PubMed: 40403939
Suppression of FOXO1 activity by SIRT1-mediated deacetylation weakening the intratumoral androgen autocrine function in glioblastoma [ Cancer Gene Ther, 2025, 32(3):343-354]	PubMed: 40075208
Mealworm hydrolysate ameliorates dexamethasone-induced muscle atrophy via sirtuin 1-mediated signaling and Akt pathway [ NPJ Sci Food, 2025, 9(1):72]	PubMed: 40360542
Neutrophils shape the therapeutic efficacy of sirtuin 1 activity modulators in murine influenza virus infection [ Biochim Biophys Acta Mol Basis Dis, 2025, 1871(7):167915]	PubMed: 40419167
Transcriptional Repression of CCL2 by KCa3.1 K+ Channel Activation and LRRC8A Anion Channel Inhibition in THP-1-Differentiated M2 Macrophages [ Int J Mol Sci, 2025, 26(15)7624]	PubMed: 40806751
Multitargeted biological actions of polydatin in preventing pseudogout acute attack [ Front Mol Biosci, 2025, 12:1553912]	PubMed: 40083631

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。