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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
Structure of SALIRASIB

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+

HIDE SMILES / InChI

Molecular Formula C22H30O2S
Molecular Weight 358.537
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 2
Optical Activity NONE

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

Approval Year

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Dislodgment and accelerated degradation of Ras.
1998 Feb 3
Farnesyl-L-cysteine analogs block SAM-induced Parkinson's disease-like symptoms in rats.
2000 Aug
Simvastatin suppresses LPS-induced MMP-1 expression in U937 mononuclear cells by inhibiting protein isoprenylation-mediated ERK activation.
2008 Oct
A phase II trial of Salirasib in patients with lung adenocarcinomas with KRAS mutations.
2011 Aug
Rosiglitazone suppresses lipopolysaccharide-induced matrix metalloproteinase-2 activity in rat aortic endothelial cells via Ras-MEK1/2 signaling.
2012 Jun 28
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
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:26:47 GMT 2023
Edited
by admin
on Fri Dec 15 16:26:47 GMT 2023
Record UNII
MZH0OM550M
Record Status Validated (UNII)
Record Version
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Name Type Language
SALIRASIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
SALIRASIB [USAN]
Common Name English
Salirasib [WHO-DD]
Common Name English
FARNESYLTHIOSALICYLATE
Systematic Name English
S-Farnesylthiosalicylic acid
Systematic Name English
salirasib [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 231306
Created by admin on Fri Dec 15 16:26:47 GMT 2023 , Edited by admin on Fri Dec 15 16:26:47 GMT 2023
EU-Orphan Drug EU/3/11/871
Created by admin on Fri Dec 15 16:26:47 GMT 2023 , Edited by admin on Fri Dec 15 16:26:47 GMT 2023
NCI_THESAURUS C1902
Created by admin on Fri Dec 15 16:26:47 GMT 2023 , Edited by admin on Fri Dec 15 16:26:47 GMT 2023
Code System Code Type Description
PUBCHEM
5469318
Created by admin on Fri Dec 15 16:26:47 GMT 2023 , Edited by admin on Fri Dec 15 16:26:47 GMT 2023
PRIMARY
USAN
SS-64
Created by admin on Fri Dec 15 16:26:47 GMT 2023 , Edited by admin on Fri Dec 15 16:26:47 GMT 2023
PRIMARY
NCI_THESAURUS
C71146
Created by admin on Fri Dec 15 16:26:47 GMT 2023 , Edited by admin on Fri Dec 15 16:26:47 GMT 2023
PRIMARY
EPA CompTox
DTXSID501025654
Created by admin on Fri Dec 15 16:26:47 GMT 2023 , Edited by admin on Fri Dec 15 16:26:47 GMT 2023
PRIMARY
SMS_ID
100000177250
Created by admin on Fri Dec 15 16:26:47 GMT 2023 , Edited by admin on Fri Dec 15 16:26:47 GMT 2023
PRIMARY
FDA UNII
MZH0OM550M
Created by admin on Fri Dec 15 16:26:47 GMT 2023 , Edited by admin on Fri Dec 15 16:26:47 GMT 2023
PRIMARY
CAS
162520-00-5
Created by admin on Fri Dec 15 16:26:47 GMT 2023 , Edited by admin on Fri Dec 15 16:26:47 GMT 2023
PRIMARY
INN
8825
Created by admin on Fri Dec 15 16:26:47 GMT 2023 , Edited by admin on Fri Dec 15 16:26:47 GMT 2023
PRIMARY
ChEMBL
CHEMBL23293
Created by admin on Fri Dec 15 16:26:47 GMT 2023 , Edited by admin on Fri Dec 15 16:26:47 GMT 2023
PRIMARY
DRUG BANK
DB12681
Created by admin on Fri Dec 15 16:26:47 GMT 2023 , Edited by admin on Fri Dec 15 16:26:47 GMT 2023
PRIMARY
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