Salirasib

製品コードS7684 バッチS768401

印刷

化学情報

Chemical Structure Synonyms Farnesylthiosalicylic acid, FTS Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C22H30O2S
分子量 358.54 CAS No. 162520-00-5
Solubility (25°C)* 体外  
 
 
* <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.

生物活性

製品説明 Salirasib (Farnesylthiosalicylic acid, FTS) is a potent competitive prenylated protein methyltransferase (PPMTase) inhibitor with Ki of 2.6 μM, which inhibits Ras methylation. Salirasib exerts antitumor effects and induces autophagy. Phase 2.
in vitro Salirasib inhibits the growth of human Ha-ras-transformed Rat1 cells, which correlates well with their inhibition for PPMTase. [1] Salirasib inhibits Ras methylation in Rat-1 fibroblasts, Ras-transformed Rat-1, and B16 melanoma cells. Salirasib also reduces the levels of Ras in cell membranes and inhibits Ras-dependent cell growth, independently of methylation, but via modulation of Ras-Raf communication. [2] In Ras-transformed EJ cells, Salirasib interferes with the activation of Raf-1 and MAPK and inhibits DNA synthesis. [3]
in vivo In Panc-1 xenografted nude mice, Salirasib (5 mg/kg i.p.) markedly inhibits tumor growth without systemic toxicity. [4] In male Wistar rats, Salirasib (5 mg/kg i.p.) markedly inhibits thioacetamide-induced -induced liver cirrhosis. [5] In the dy(2J)/dy(2J) mouse model of congenital muscular dystrophy, Salirasib (5 mg/kg i.p.) attenuates fibrosis and improves muscle strength. [6]

プロトコル(参考用のみ)

キナーゼアッセイ PPMTase Assays
Synaptosomal membranes of rat brain cerebellum or total membranes of cultured cell lines (100,000 × g pellet) are used for methyltransferase assays in the cell-free systems. Methyltransferase assays are performed at 37°C in 50 mM Tris-HCl buffer, pH 7.4, using 100 μg of protein, 25 μM [methyl-3H]AdoMet (300,000 cpm/nmol), and 50 μM AFC (prepared as a stock solution in DMSO) in a total volume of 50 μL. DMSO concentration in all assays is 8%. Various AFC concentrations are used in several experiments as indicated in the text. Reactions are terminated after 10 min by addition of 500 μL of chloroform:methanol (1:1) with subsequent addition of 250 μL of H2O, mixing, and phase separation. A 125-μL portion of the chloroform phase is dried at 40°C, and 200 μl of 1 N NaOH, 1% SDS solution is added. The methanol thus formed is counted by the vapor phase equilibrium method. Typical background counts (no AFC added) are 50-100 cpm, while typical reactions with AFC yield 500-6,000 cpm. Assays are performed in triplicate, and background counts are subtracted. Methylation of endogenous substrates and gel electrophoresis are performed. Protein carboxyl methylation in intact cells is determined using 100 μCi/mL [methyl-3H]methionine. Cells are assayed in near confluent cultures grown in 10-cm plates with 5 mL of labeling medium.
細胞アッセイ 細胞株 PC12, CHE, T-antigen-transformed CHE, endothelial cells, astrocytes, B16, Rat1, EJ, NIH3T3, v-Raf-transformed NIH3T3 cell lines
濃度 ~100 μM
反応時間 10 days
実験の流れ Cells are grown in 24-well plates. 2 h after plating, the cells receive either solvent or FTS freshly prepared from a stock solution to yield the final indicated concentrations in 0.1% DMSO. Media are replaced every 4 days with fresh medium containing the solvent or the drug. Separate experiments indicate that the solvent itself has no effect on cell growth. On the indicated days, the cells are detached from plates by trypsin/EDTA and counted under the light microscope. All assays are performed in quadruplicate. In parallel experiments, cells are stained either with trypan blue or with MTT, and the stained cells are examined under the light microscope. In some MTT-stained cultures, the cells are dissolved in 0.2 mL of 100% DMSO, and the extent of staining is determined spectrophotometrically using an enzyme-linked immunosorbent assay reader.
動物実験 動物モデル Panc-1 xenografted nude mice
投薬量 5 mg/kg daily
投与方法 i.p.

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：

Crosstalk between protein kinase C α and transforming growth factor β signaling mediated by Runx2 in intestinal epithelial cells [ J Biol Chem, 2023, 299(4):103017] PubMed: 36791912
Vemurafenib Inhibits Acute and Chronic Enterovirus Infection by Affecting Cellular Kinase Phosphatidylinositol 4-Kinase Type IIIβ [ Microbiol Spectr, 2023, 11(4):e0055223] PubMed: 37436162
BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy [ Nat Commun, 2022, 13(1):7113] PubMed: 36402789
ATAD3A mediates activation of RAS-independent mitochondrial ERK1/2 signaling, favoring head and neck cancer development [ J Exp Clin Cancer Res, 2022, 41(1):43] PubMed: 35093151
A novel antiproliferative PKCα-Ras-ERK signaling axis in intestinal epithelial cells [ J Biol Chem, 2022, 298(7):102121] PubMed: 35697074
Oxymatrine Inhibits Proliferation and Migration of Vulvar Squamous Cell Carcinoma Cells via Attenuation of the RAS/RAF/MEK/ERK Pathway [ Cancer Manag Res, 2020, 12:2057-2067] PubMed: 32256113
MAPK inhibitors induce serine peptidase inhibitor Kazal type 1 (SPINK1) secretion in BRAF V600E-mutant colorectal adenocarcinoma. [ Mol Oncol, 2018, 12(2):224-238] PubMed: 29193645
Dasatinib synergizes with ATRA to trigger granulocytic differentiation in ATRA resistant acute promyelocytic leukemia cell lines via Lyn inhibition-mediated activation of RAF-1/MEK/ERK [ Food Chem Toxicol, 2018, 119:464-478] PubMed: 29097117
The dynamics of ERK signaling in melanoma, and the response to BRAF or MEK inhibition, are cell cycle dependent [ SSRN, 2018, 10.2139/ssrn.3188455] PubMed: None
The N-terminal tail coordinates with carbohydrate recognition domain to mediate galectin-3 induced apoptosis in T cells. [ Oncotarget, 2017, 8(30):49824-49838] PubMed: 28548942

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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