Salirasib
(Synonyms: 法尼基硫代水杨酸; S-Farnesylthiosalicylic acid; Farnesyl Thiosalicylic Acid; FTS) 目录号 : GC10528A Ras inhibitor with anti-cancer and anti-atherogenic activity
Cas No.:162520-00-5
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
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Cell experiment: | For time dependent response studies, cells are harvested with 0.05% Trypsin-EDTA daily for 1 to 7 days and counted under the microscope using the Trypan blue exclusion method.For dose response studies, cells are incubated in medium supplemented with salirasib or DMSO for 3 days. Cell viability is determined using a colorimetric WST-1 assay according to the manufacturer's instructions. The IC50 value, at which 50% of the cell growth is inhibited compared with DMSO control, is calculated by nonlinear regression analysis using GraphPad Prism software. |
Animal experiment: | Six week old female athymic NMRI nu/nu mice are housed in filter-topped cages andreceive food and water ad libitum. Tumors are generated by subcutaneous injection into the right lower flank with 5×106 HepG2 cells suspended in 100 μL PBS in 12 mice. Two weeks after cell inoculation, when palpable tumours are established, mice are separated into salirasib-treated (n=6) and control group (n=4). Two animals do not develop tumours at that time point and had to be excluded from the study. They receive daily i.p. injections of 10 mg/kg salirasib or a similar volume of vehicle solution (PBS containing 2.5% v/v ethanol, pH 8.0) for 12 days. Tumor dimensions are recorded three times per week with a digital calliper starting with the first day of treatment. Tumor volumes are estimated as follows: V (mm3)=(length×width2)/2. Tumour weights are recorded at the time of sacrifice in order to evaluate treatment response. |
References: [1]. Makovski V, et al. Farnesylthiosalicylic acid (salirasib) inhibits Rheb in TSC2-null ELT3 cells: a potential treatment for lymphangioleiomyomatosis. Int J Cancer. 2012 Mar 15;130(6):1420-9. |
Salirasib (S-trans,trans-farnesylthiosalycilic acid [FTS]) is a synthetic small molecule that acts as a potent Ras inhibitor.[1]
The Ras family of small GTPases transmits extracellular signals, which are initiated by cell-surface receptors and serve to regulate various cellular processes including cell growth, differentiation, motility and cell death. Signals transmitted by activated Ras induce activation of multiple effectors. Ras signaling is activated in a large number of human cancers. Mutations of codons 12, 13 and 61 in Ras result in constitutively active Ras, and activating mutations of the three major Ras isoforms (H, K and N) have been found in more than 33% of human cancers. [2]
Salirasib mimics the carboxy-terminal farnesylcysteine carboxymethyl ester common to all Ras proteins, which acts as part of a recognition unit for anchorage and dislodges the active Ras protein from the cell membrane. Salirasib is readily taken up by cells, and once inside the cell it specifically disrupts the association of active forms of all Ras proteins (H-ras, K-ras and N-ras) with the inner surface of the cell membrane and with other cellular membranes. [1]
The in vitro activity of salirasib has been demonstrated in pancreatic cell lines and xenograft models. In the Panc-1 cell line, salirasib decreased the amount of RAS in a dosedependent manner, with a maximum decrease in Ras of approximately 50 % seen at concentrations of 25 to 50 μM. In the mouse xenograft models, salirasib inhibites Panc-1 tumor growth and is shown to be synergistic with gemcitabine, both inhibiting tumor growth and prolonging survival. Salirasib is tested in a phase I study in patients with solid tumors twice daily for 21 days every 4 weeks. Doses are escalated from 100 to 200, 400, 600, and 800 mg. Dose-limiting toxicity is not reached, but all three patients treated with 800 mg experienced Grade 1–2 diarrhea, preventing further dose escalation. The recommended dose for phase II studies is 600 mg bid. [3]
References:
[1] Ernesto Bustinza-Linares, Razelle Kurzrock , Apostolia-Maria Tsimberidou. Salirasib in the treatment of pancreatic cance. Future Oncol. (2010) 6(6), 885–891.
[2] Sari Schokoroy, Dolly Juster, Yoel Kloog, Ronit Pinkas-Kramarski. Disrupting the Oncogenic Synergism between Nucleolin and Ras Results in Cell Growth Inhibition and Cell Death. PLOS ONESeptember 2013, Volume 8, Issue 9, e75269.
[3] Daniel Laheru , Preeti Shah, N. V. Rajeshkumar et al. Integrated preclinical and clinical development of S-trans, trans-farnesylthiosalicylic acid (FTS, Salirasib) in pancreatic cancer. Invest New Drugs (2012) 30:2391–2399.
Cas No. | 162520-00-5 | SDF | |
别名 | 法尼基硫代水杨酸; S-Farnesylthiosalicylic acid; Farnesyl Thiosalicylic Acid; FTS | ||
化学名 | 2-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl]sulfanylbenzoic acid | ||
Canonical SMILES | CC(=CCCC(=CCCC(=CCSC1=CC=CC=C1C(=O)O)C)C)C | ||
分子式 | C22H30O2S | 分子量 | 358.54 |
溶解度 | ≥ 16.75 mg/mL in DMSO, ≥ 16.2 mg/mL in EtOH | 储存条件 | Store at -20°C |
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Shipping Condition | 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。 |
制备储备液 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.7891 mL | 13.9454 mL | 27.8909 mL |
5 mM | 0.5578 mL | 2.7891 mL | 5.5782 mL |
10 mM | 0.2789 mL | 1.3945 mL | 2.7891 mL |
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