Salirasib Chemical Properties

Melting point:

64-66°C

Boiling point:

486.0±45.0 °C(Predicted)

Density 

1.05

storage temp. 

-20°C

solubility 

DMSO: soluble20mg/mL, clear

pka

3.50±0.36(Predicted)

form 

powder

color 

white to beige

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.

InChI

InChI=1S/C22H30O2S/c1-17(2)9-7-10-18(3)11-8-12-19(4)15-16-25-21-14-6-5-13-20(21)22(23)24/h5-6,9,11,13-15H,7-8,10,12,16H2,1-4H3,(H,23,24)/b18-11+,19-15+

InChIKey

WUILNKCFCLNXOK-CFBAGHHKSA-N

SMILES

C(O)(=O)C1=CC=CC=C1SC/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/C

Safety Information

HS Code 

2930.90.2900

Salirasib Usage And Synthesis

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 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

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 has been used as a farnesyltransferase inhibitor.

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] DANIELLA MARCIANO. Farnesyl Derivatives of Rigid Carboxylic Acids - Inhibitors of ras-Dependent Cell Growth[J]. Journal of Medicinal Chemistry, 1995, 38 8: 1267-1272. DOI:10.1021/jm00008a004
[2] Selective inhibition of Ras-dependent cell growth by farnesylthiosalicylic acid (salirasib) in patients with solid tumors
[3] RONI HAKLAI. Dislodgment and Accelerated Degradation of Ras†[J]. Biochemistry Biochemistry, 1998, 37 5: 1306-1314. DOI:10.1021/bi972032d
[4] DANIEL LAHERU. Integrated preclinical and clinical development of S-trans, trans-Farnesylthiosalicylic Acid (FTS, Salirasib) in pancreatic cancer.[J]. Investigational New Drugs, 2012: 2391-2399. DOI:10.1007/s10637-012-9818-6
[5] APOSTOLIA MARIA TSIMBERIDOU. Phase 1 first-in-human clinical study of S-trans,trans-farnesylthiosalicylic acid (salirasib) in patients with solid tumors.[J]. Cancer Chemotherapy and Pharmacology, 2010, 65 2: 235-241. DOI:10.1007/s00280-009-1027-4
[6] N CHARETTE. Salirasib sensitizes hepatocarcinoma cells to TRAIL-induced apoptosis through DR5 and survivin-dependent mechanisms[J]. Cell Death & Disease, 2013, 4 1: e471-e471. DOI:10.1038/cddis.2012.200
[7] MICHAEL MAHER. Activation of TRPA1 by farnesyl thiosalicylic acid.[J]. Molecular Pharmacology, 2008, 73 4: 1225-1234. DOI:10.1124/mol.107.042663

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