Salirasib是一种有效的竞争性
prenylated protein methyltransferase (PPMTase)抑制剂， K
i为2.6 μM，其抑制
Ras甲基化。Phase 2。
Salirasib inhibits the growth of human Ha-ras-transformed Rat1 cells, which correlates well with their inhibition for PPMTase. Salirasib inhibits Ras methylation in Rat-1 fibroblasts, Ras-transformed Rat-1, and B16 melanoma cells. Salirasib also reduces the levels of Ras in cell membranes and inhibits Ras-dependent cell growth, independently of methylation, but via modulation of Ras-Raf communication. In Ras-transformed EJ cells, Salirasib interferes with the activation of Raf-1 and MAPK and inhibits DNA synthesis.
In Panc-1 xenografted nude mice, Salirasib (5 mg/kg i.p.) markedly inhibits tumor growth without systemic toxicity. In male Wistar rats, Salirasib (5 mg/kg i.p.) markedly inhibits thioacetamide-induced -induced liver cirrhosis. In the dy(2J)/dy(2J) mouse model of congenital muscular dystrophy, Salirasib (5 mg/kg i.p.) attenuates fibrosis and improves muscle strength.
Salirasib (Farnesylthiosalicylic acid, FTS)是一种有效的竞争性prenylated protein methyltransferase (PPMTase)抑制剂， Ki为2.6 μM，其抑制Ras甲基化。Salirasib 具有抗肿瘤的活性并可诱导凋亡。Phase 2。
| Target | Value |
Ras
()
|
|
PPMTase
()
|
2.6 μM(Ki)
|
Salirasib抑制人Ha-ras转化的Rat1细胞生长，这与它们对PPMTase的抑制良好相关。 Salirasib抑制Rat-1成纤维细胞，Ras转化的Rat-1，以及B16黑色素瘤细胞中Ras甲基化。Salirasib也会降低细胞膜中Ras水平，并抑制Ras依赖性细胞生长，其独立于甲基化，但是由Ras-Raf通讯调节。在Ras转化的EJ细胞中，Salirasib干扰Raf-1 和MAPK活化，并抑制DNA合成。
在Panc-1异种移植的裸鼠体内，Salirasib (5 mg/kg i.p.)显著抑制肿瘤生长，而没有全身毒性。在雄性Wistar大鼠体内，Salirasib (5 mg/kg i.p.)显著抑制硫代乙酰胺诱导的肝硬化。在先天性肌营养不良的dy(2J)/dy(2J)小鼠模型中，Salirasib (5 mg/kg i.p.)减弱纤维化，并提高肌肉力量。
