Salirasib

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Chemical Structure| 162520-00-5 同义名 : 沙利雷塞 ;S-Farnesylthiosalicylic acid;Farnesyl Thiosalicylic Acid;FTS
CAS号 : 162520-00-5
货号 : A100859
分子式 : C22H30O2S
纯度 : 98%
分子量 : 358.537
MDL号 : -
存储条件：

Pure form Sealed in dry,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(139.46 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The free carboxyl group of the terminal farnesylcysteine or geranylgeranylcysteine in a large number of prenylated proteins is methylated by the prenylated protein methyltransferase (PPMTase), a unique enzyme among methyltransferases and this enzyme tightly associates with the particulate fractions in eukaryotic cells. Ras proteins are members of a family of GTPases that are essential components of receptor-mediated signaling cascades which regulate cell growth and differentiation and are also important components of signaling pathways that regulate cell death, cell shape and cell motility. Salirasib (S-trans,trans-Farnesylthiosalicylic acid (FTS)), a novel farnesylated rigid carboxylic acid derivative, acts as a potent competitive inhibitor of PPMTase with Ki of 2.6 mM. Salirasib inhibited the growth of human Ha-ras-transformed Rat1 cells in vitro with EC50 of 7.5 μM[3]. In Panc-1 cells, FTS at a concentration of 25 – 100 mM reduced the amount of Ras in a dose-dependent manner[4]. Daily FTS treatment (5 mg/kg intraperitoneally) in Panc-1 xenografted mice markedly decreased tumor growth (after treatment for 18 days, tumor volume had increased by only 23 ± 30-fold in the FTS-treated group and by 127 ± 66-fold in controls)[4]. Salirasib reduced survivin expression in a time- and dose-dependent manner. After 48h of incubation with 150 mM of salirasib, mRNA levels of survivin decreased by 60, 70 and 45% in HepG2, Hep3B and Huh7, respectively[5]. 9L gliosarcoma cells established tumor-bearing rats were treated with convection enhanced drug delivery (CED) of salirasib (50 μM), at 10 days, average tumor growth rates (normalized in each rat to the initial tumor volume and then averaged over the group of rats) was1.61 ± 0.32 in salirasib-treated rats compared with 3.22 ± 0.55 in control[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.79mL

0.56mL

0.28mL

13.95mL

2.79mL

1.39mL

27.89mL

5.58mL

2.79mL
参考文献

[1]Weisz B, Giehl K, et al. A new functional Ras antagonist inhibits human pancreatic tumor growth in nude mice. Oncogene. 1999 Apr 22;18(16):2579-88.

[2]Marciano D, Ben-Baruch G, et al. Farnesyl derivatives of rigid carboxylic acids-inhibitors of ras-dependent cell growth. J Med Chem. 1995 Apr 14;38(8):1267-72.

[3]Marciano D, Ben-Baruch G, Marom M, Egozi Y, Haklai R, Kloog Y. Farnesyl derivatives of rigid carboxylic acids-inhibitors of ras-dependent cell growth. J Med Chem. 1995 Apr 14;38(8):1267-72. doi: 10.1021/jm00008a004. PMID: 7731012.

[4]Weisz B, Giehl K, Gana-Weisz M, Egozi Y, Ben-Baruch G, Marciano D, Gierschik P, Kloog Y. A new functional Ras antagonist inhibits human pancreatic tumor growth in nude mice. Oncogene. 1999 Apr 22;18(16):2579-88. doi: 10.1038/sj.onc.1202602. PMID: 10353601.

[5]Charette N, De Saeger C, Horsmans Y, Leclercq I, Stärkel P. Salirasib sensitizes hepatocarcinoma cells to TRAIL-induced apoptosis through DR5 and survivin-dependent mechanisms. Cell Death Dis. 2013 Jan 24;4(1):e471. doi: 10.1038/cddis.2012.200. PMID: 23348585; PMCID: PMC3563988.

[6]Goldberg L, Ocherashvilli A, Daniels D, Last D, Cohen ZR, Tamar G, Kloog Y, Mardor Y. Salirasib (farnesyl thiosalicylic acid) for brain tumor treatment: a convection-enhanced drug delivery study in rats. Mol Cancer Ther. 2008 Nov;7(11):3609-16. doi: 10.1158/1535-7163.MCT-08-0488. PMID: 19001442.