FTI 277 HYDROCHLORIDE

FTI 277 HCl是FTI 277的甲酯，是一种有效的选择性farnesyltransferase (FTase)抑制剂，IC50为500 pM，选择性比密切相关的GGTase I 高100倍。 FTI-277 inhibits Ras processing with an IC50 of 100 nM, but not the geranylgeranylated Rap1A processing in whole cells. FTI-277 induces accumulation of cytoplasmic non-farnesylated H-Ras, accumulates inactive Ras/Raf complexes in the cytoplasm, and blocks constitutive MAPK activation in H-RasF cells. FTI-277 causes increased apoptosis after irradiation and increases radiosensitivity in H-ras-transformed rat embryo cells. FTI-277 also inhibits cell growth and induces apoptosis in drug-resistant myeloma tumor cells. In SH-SY5Y cells, FTI-277 diminishes the toxic effects of methamphetamine on induction in cell degeneration, activation in c-Jun-N-terminal kinase cascades, and Ras activation. In mice coinfected with hepatitis B virus (HBV) and HDV, FTI-277 (50 mg/kg/d i.p.) effectively clears HDV viremia. FTI 277 HCl是FTI 277的甲酯，是一种有效的选择性farnesyltransferase (FTase)抑制剂，IC50为500 pM，选择性比密切相关的GGTase I 高100倍。FTI 277 HCl可抑制细胞生长并诱导凋亡。FTI 277 HCl可有效清除HDV病毒血症。

Target	Value
FTase (Cell-free assay)	500 pM

FTI-277抑制Ras加工，IC50 为100 nM，但不抑制全细胞中四异戊二烯化Rap1A加工。FTI-277诱导细胞质非法尼化H-Ras积累，在细胞质中积累无活性的Ras/Raf，并阻断H-RasF细胞中组成型MAPK激活。 FTI-277引起辐射后细胞凋亡增加，并增加H-ras转化的大鼠胚胎细胞的辐射敏感性。在耐药骨髓瘤细胞中，FTI-277也会抑制细胞生长，并诱导细胞凋亡。在SH-SY5细胞中，FTI-277减少细胞退化，活化，c-Jun-N端激酶级联和Ras激活过程中甲基苯丙胺诱导的毒性作用。

在感染乙型肝炎病毒(HBV) 和 HDV的小鼠体内，FTI-277 (50 mg/kg/d i.p.)有效清除HDV病毒血症。