162520-00-5

Basic information

• Product Name: Salirasib
• Synonyms: FARNESYLTHIOSALICYLIC ACID;FTS;(3,7,11-TRIMETHYLDODECA-2,6,10-TRIENYL)-2-THIOBENZOIC ACID;Unii-mzh0om550m;2-[[(2E,6E)-3,7,11-Trimethyl-2,6,10-dodecatrien-1-yl]thio]benzoic acid;Farnesylthiosalicylate;Salirasib;S-Farnesylthiosalicylic acid
• CAS NO: 162520-00-5
• Molecular Formula: C22H30O2S
• Molecular Weight: 358.54
• Product Categories: API;Aromatics;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 162520-00-5.mol
• Article Data: 9

Chemical Properties

• Melting Point: 64-66°C
• Boiling Point: 486.0±45.0 °C(Predicted)
• Appearance: white to beige/
• Density: 1.05
• Storage Temp.: -20°C Freezer
• Solubility: DMSO: soluble20mg/mL, clear
• PKA: 3.50±0.36(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: Salirasib(CAS DataBase Reference)
• NIST Chemistry Reference: Salirasib(162520-00-5)
• EPA Substance Registry System: Salirasib(162520-00-5)

Safety Data

• Hazardous Substances Data: 162520-00-5(Hazardous Substances Data)

Usage

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 IC50 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 Ki 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

Different sources of media describe the Uses of 162520-00-5 differently. You can refer to the following data:
1. 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.
2. 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.
3. Salirasib has been used as a farnesyltransferase inhibitor.

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

Upstream product

• 4602-84-0 farnesol 
• 24163-93-7 farnesyl bromide 
• 118-92-3 anthranilic acid 
• 147-93-3 Thiosalicylic acid 
• 6784-45-8 1-chloro-3,7,11-trimethyldodeca-2,6,10-triene 
• 6784-45-8 (2E,6E)-farnesyl chloride 
• 4892-02-8 Methyl thiosalicylate 
• 7283-41-2 thiosalicilyc acid 
• 3796-70-1 trans geranyl acetone 
• 24163-93-7 farnesyl bromide 
• 106-28-5 Farnesol 
• 19954-66-6 ethyl farnesoate 

Downstream Products

• 1611453-61-2 N-(2-(diethylamino)ethyl)-2-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)thio)benzamide 
• 1402249-31-3 N-(3-(dimethylamino)propyl)-2-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)thio)benzamide 
• 1402249-32-4 N-(3-(diethylamino)propyl)-2-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)thio)benzamide 
• 1402249-35-7 N-(4-(diethylamino)butyl)-2-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)thio)benzamide 
• 1402249-43-7 N-(2-((2-hydroxyethyl)amino)ethyl)-2-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)thio)benzamide 
• 1611453-62-3 N-(2-(bis(2-hydroxyethyl)amino)ethyl)-2-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)thio)benzamide 
• 1611453-63-4 N-(2-(2-hydroxyethoxy)ethyl)-2-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)thio)benzamide 
• 1613704-80-5 2-methoxy-4-((E)-3-oxo-3-(4-(4-benzylpiperazin-1-yl)butoxy)-prop-1-enyl)phenyl-2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-tri-enylthio)benzoate 
• 1613704-81-6 4-((E)-3-(4-(1H-imidazol-1-yl)butoxy)-3-oxoprop-1-enyl)-2-methoxyphenyl-2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)benzoate 
• 1613704-82-7 4-((E)-3-oxo-3-(4-(piperidin-1-yl)butoxy)prop-1-en-1-yl)phenyl-2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)benzoate 
• 1613704-83-8 4-((E)-3-(4-morpholinobutoxy)-3-oxoprop-1-enyl)phenyl-2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)benzoate 
• 1613704-84-9 4-((E)-3-(4-(4-methylpiperazin-1-yl)butoxy)-3-oxoprop-1-enyl)-phenyl-2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)benzoate 
• 1613704-85-0 4-((E)-3-oxo-3-(4-(4-phenylpiperazin-1-yl)butoxy)prop-1-enyl)-phenyl-2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)benzoate 
• 1613704-86-1 tert-butyl 4-(4-((E)-3-(4-(2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)benzoyloxy)phenyl)acryloyloxy)butyl)piperazine-1-carboxylate 

Relevant articles and documents

Hybrids from farnesylthiosalicylic acid and hydroxamic acid as dual ras-related signaling and histone deacetylase (HDAC) inhibitors: Design, synthesis and biological evaluation

Abstract A novel series of hybrids was designed and synthesized by combining key elements from farnesylthiosalicylic acid (FTS) and hydroxamic acid. Several 3,7,11-trimethyldodeca-2,6, 10-trien-1-yl) thio)benzamide derivatives, particularly those with bra

Repositioning Salirasib as a new antimalarial agent

Malaria is a serious tropical disease that kills thousands of people every year, mainly in Africa, due to Plasmodium falciparum infections. Salirasib is a promising cancer drug candidate that interferes with the post-translational modification of Ras. This S-farnesyl thiosalicylate inhibits isoprenylcysteine carboxyl methyltransferase (ICMT), a validated target for cancer drug development. There is a high homology between the human and the parasite enzyme isoforms, in addition to being a druggable target. Looking to repurpose its structure as an antimalarial drug, a collection of S-substituted derivatives of thiosalicylic acid were prepared by introducing 1,2,3-triazole as a diversity entry point or by direct alkylation of the thiol. We further investigated the in vitro toxicity of FTS analogues to Plasmodium falciparum in the asexual stages and in Vero cells. An antiplasmodial activity assay was performed using a simple, high-sensitivity methodology based on nanoluciferase (NLuc)-transfected P. falciparum parasites. The results showed that some of the analogs were active at low micromolar concentration, including Salirasib. The most potent member of the series has S-farnesyl and the 1,2,3-triazole moiety substituted with phytyl. However, the compound substituted with methyl-naphthyl shows promising physicochemical and activity values. The low cytotoxicity in eukaryotic cells of the most active analogs provided good therapeutic indices, being starting-point candidates for future antimalarial drug development.

Hybrid molecule from Farnesylthiosalicylic acid-diamine and phenylpropenoic acid as Ras-related signaling inhibitor with potent antitumor activities

Novel series of Farnesylthiosalicylic acid-diamine/phenylpropenoic acid hybrids were designed and synthesized. Their in vitro growth inhibitory assays showed that most compounds displayed strong antiproliferation activity against seven cancer cells. Especially, the new hybrid 12f, by the conjugation of 10a with ferulic acid, could selectively suppress the proliferation of tumor cells and display significantly lower toxicities to normal cells than its intermediate 10a. Furthermore, 12f dose-dependently induced SMMC-7721 cell apoptosis. Additionally, our observations demonstrated that 12f inhibited both Ras-related signaling and phosphorylated NF-κB synergistically, which may be advantageous to the strong antitumor activities of 12f. Our findings suggest that these novel hybrids may hold a great promise as therapeutic agents for the intervention of human cancers.