Description
Association of Ras protein with the inner surface of the plasma membrane is required for Ras signaling activity. Farnesyl thiosalicylic acid (FTS) is an inhibitor of Ras-
mediated signaling that functions by dislodging Ras from the cell membrane thereby rendering it susceptible to proteolytic degradation. FTS inhibits the growth of human Ha-
ras-
transformed Rat1 fibroblasts with an IC
50 value of 7.5 μM. It does not inhibit Ras farnesylation
in vitro and although FTS does inhibit prenylated protein methyltransferase (PPMTase) in cell-
free systems with a K
i value of 2.6 μM, it is relatively ineffective at inhibiting methylation in whole cells. Treatment of chow-
fed ApoE-
deficient mice with 5 mg/kg FTS three times per week for six weeks reduces early atherosclerotic lesion development by 52% compared to controls.
Chemical Properties
Pale Yellow Solid
Uses
Salirasib has been used as a farnesyltransferase inhibitor.
Uses
It is a new specific nontoxic drug with a mild hydrophobic nature, which acts as a Ras antagonist and can therefore be used for stent applications as well as for local cancer treatment.
Uses
Salirasib is a new specific nontoxic drug with a mild hydrophobic nature, which acts as a Ras antagonist and can therefore be used for stent applications as well as for local cancer treatment.
Definition
ChEBI: Salirasib is a sesquiterpenoid.
Biochem/physiol Actions
Salirasib (Farnesylthiosalicylic acid) is a RAS inhibitor that acts by dislodging the farnesylated protein from the membrane, facilitating Ras degradation. Salirasib impairs downstream signaling and suppresses growth and migration of proliferating tumor cells in in vitro and in vivo models. Salirasib (Farnesylthiosalicylic acid) has recently been shown to possess significant anti-inflammatory and anti-arthritic properties.
References
1) Marciano?et al. (1995),?Farnesyl Derivatives of Rigid Carboxylic Acids – Inhibitors of ras-Dependent Cell Growth; J. Med. Chem.,?38?1267
2) Marom?et al. (1995),?Selective inhibition of Ras-dependent cell growth by farnesylthiosalicylic acid (salirasib) in patients with solid tumors; J. Biol. Chem.,?270?22263
3) Haklai?et al. (1998),?Dislodgement and Accelerated Degradation of Ras; Biochemistry,?37?1306
4) Laheru?et al. (2012),?Integrated preclinical and clinical development of S-trans,trans-Farnesylthiosalicylic acid (FTS, Salirasib) in pancreatic cancer; Invest .New Drugs,?30?2391
5) Tsimberidou?et al. (2010),?Phase 1 first-in-human clinical study of S-trans,trans-farnesylthiosalicylic acid (salirasib) in patients with solid tumors; Cancer Chemother. Pharmacol.,?65?235
6) Charette?et al. (2013),?Salirasib sensitizes hepatocarcinoma cells to TRAIL-induced apoptosis through DR5 and survivin-dependent mechanisms; Cell Death and Disease.?4?e471
7) Maher?et al. (2008),?Activation of TRPA1 by farnesyl thiosalicylic acid; Mol. Pharmacol.,?73?1225
