"目录号: HY-14754

GPCR/G ProteinAutophagy-

Salirasib 是一种有效的，竞争性的PPMTase抑制剂，Ki值为 2.6 μM，同时也抑制Ras甲基化。

RasAutophagy

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生物活性

Description

Salirasib is a potent and competitive?prenylated protein methyltransferase (PPMTase)?inhibitor with?Ki?of 2.6 μM, which inhibits?Ras?methylation.

IC50& Target

Ki: 2.6 μM (PPMTase)

In Vitro

Salirasib (12.5-100 μM) inhibits the proliferation of ELT3 cells in a dose-dependent manner with an average IC50of 58.57±4.59 μM. The effects of Salirasib on the TSC2-null cells are evidently mimicked by DN-Rheb but not by DN-Ras. Salirasib reduces Rheb in TSC2-null cells and TSC2 expression rescues the cells from the inhibitory effect of Salirasib. Salirasib reduces phosphorylation of S6K but not of ERK in the TSC2-null ELT3 cells[1]. Salirasib (50, 100, 150 μM) induces a dose- and time-dependent decrease of cell growth in HCC cells. Salirasib reduces cell proliferation through modulation of cell cycle effectors and inhibitors. Salirasib induces apoptosis in HepG2 and Hep3B cells. The growth inhibitory effect of salirasib in HCC cell lines is associated with mTOR inhibition independent of ERK or Akt activation[2].

In Vivo

Salirasib (40, 60 or 80 mg/kg, p.o.) significantly inhibits the tumor growth in a dose dependent manner in vivo[1]. Salirasib (5 mg/kg, i.p.) significantly decreases Ras expression in thedy2J/dy2Jmice, and causes an increase in Ras expression which is by far much lower than the increase observed in thedy2J/dy2Jmice. Salirasib treatment is associated with significantly inhibition of both MMP-2 and MMP-9 activities in thedy2J/dy2Jmice[2]. Salirasib (10 mg/kg, i.p.) inhibits tumour growth in a subcutaneous xenograft mice model without weight loss[3].

Clinical Trial

NCT00531401

Concordia Pharmaceuticals, Inc

Carcinoma, Non-Small-Cell Lung

September 2007

Phase 2

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References

[1].Makovski V, et al. Farnesylthiosalicylic acid (salirasib) inhibits Rheb in TSC2-null ELT3 cells: a potential treatment for lymphangioleiomyomatosis. Int J Cancer. 2012 Mar 15;130(6):1420-9.

[2].Nevo Y, et al. Chapman J. The Ras antagonist, farnesylthiosalicylic acid (FTS), decreases fibrosis and improves muscle strength in dy/dy mouse model of muscular dystrophy. PLoS One. 2011 Mar 22;6(3):e18049.

[3].Charette N, et al. Salirasib inhibits the growth of hepatocarcinoma cell lines in vitro and tumor growth in vivo through ras and mTOR inhibition. Mol Cancer. 2010 Sep 22;9:256.