Details
Stereochemistry | ACHIRAL |
Molecular Formula | C22H30O2S |
Molecular Weight | 358.537 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 2 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)=CCC\C(C)=C\CC\C(C)=C\CSC1=CC=CC=C1C(O)=O
InChI
InChIKey=WUILNKCFCLNXOK-CFBAGHHKSA-N
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+
Salirasib or S-trans,trans-Farnesylthiosalicylic acid (FTS) is a salicylic acid derivative with potential antineoplastic activity. It acts as a potent competitive inhibitor of the enzyme prenylated protein methyltransferase (PPMTase), which methylates the carboxyl-terminal S-prenylcysteine in a large number of prenylated proteins including Ras. In such systems, Salirasib inhibits Ras methylation but not Ras farnesylation. Salirasib selectively disrupts the association of chronically active Ras proteins with the plasma membrane. Salirasib competes with Ras for binding to Ras-escort proteins, which possess putative farnesyl-binding domains and interact only with the activated form of Ras proteins, thereby promoting Ras nanoclusterization in the plasma membrane and robust signals. Salirasib was studied in the clinical trials in patients with solid tumors, however its development was discontinued.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7731012
Curator's Comment: 1995
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL4699 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7673206 |
2.6 µM [Ki] | ||
Target ID: GO:0007265 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Dislodgment and accelerated degradation of Ras. | 1998 Feb 3 |
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Farnesyl thiosalicylic acid chemosensitizes human melanoma in vivo. | 2003 Jan |
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The Ras inhibitor farnesylthiosalicylic acid (Salirasib) disrupts the spatiotemporal localization of active Ras: a potential treatment for cancer. | 2008 |
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Integrated Transcriptional and Proteomic Analysis of Growth Hormone Suppression Mediated by Trichothecene T-2 Toxin in Rat GH3 Cells. | 2015 Oct |
Patents
Sample Use Guides
A phase II trial of Salirasib in patients with lung adenocarcinomas with KRAS mutations. Patients were treated with salirasib 800 mg twice daily on days 1 to 28 of a 35-day cycle. The schedule of days 1 to 28 of a 35-day cycle was chosen to allow initial imaging after 4 weeks of continuous treatment. After 10 patients were enrolled, because of toxicity (described in Results), the initial dose was changed to 600 mg twice daily.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7673206
Salirasib or S-trans,trans-Farnesylthiosalicylic acid (FTS) inhibits the growth of human Ha-ras-transformed cells (EJ cells) and reverses their transformed morphology in a dose-dependent manner (0.1-10 microM). The drug does not interfere with the growth of cells transformed by v-Raf or T-antigen but inhibits the growth of ErbB2-transformed cells and blocks the mitogenic effects of epidermal and basic fibroblast growth factors, thus implying its selectivity toward Ras growth signaling, possibly via modulation of Ras-Raf communication.
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FDA ORPHAN DRUG |
231306
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EU-Orphan Drug |
EU/3/11/871
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NCI_THESAURUS |
C1902
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5469318
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SS-64
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C71146
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DTXSID501025654
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100000177250
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162520-00-5
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8825
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CHEMBL23293
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DB12681
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ACTIVE MOIETY