Telaprevir 是一种选择性可逆的HCV NS3-4A 蛋白酶抑制剂，作用于基因 1型 (H株) NS3 蛋白酶结构域和 NS4A 辅因子肽，Ki为 7 nM。它也是 SARS-CoV-2 3CLpro 抑制剂。

Telaprevir (VX-950) is an effective inhibitor of HCV NS3-4A serine protease (IC50: 0.35 μM).

在小鼠模型中, Telaprevir（10和25 mg/kg,p.o.） 降低丙型肝炎病毒蛋白酶依赖的裂解（18.7%）和SEAP（18.4%）从肝脏到血液的分泌中.在基因型1b HCV感染人肝细胞的小鼠中,Telaprevir（200 mg/kg）处理1周可使HCV RNA降低,和MK-0608（50 mg/kg）联用处理小鼠,持续4周,可完全除去鼠体内病毒.

Telaprevir （17.5 μM）完全消除复制细胞中HCV RNA,停止处理13天后也不再出现。Telaprevir和IFN-α联用可适度提高协同作用,降低HCV RNA复制并抑制耐药突变,但无明显毒性。Telaprevir时间依赖性地促进对HCV RNA复制的抑制,温育24, 48, 72和120小时,则IC50值分别为 0.574 μM, 0.488 μM, 0.210 μM和0.139 μM。在Con1(基因型 1b) 亚基因组HCV复制细胞中,Telaprevir抑制丙型肝炎病毒NS3-4A丝氨酸蛋白酶,导致病毒多聚蛋白加工受抑制,且随后使病毒RNA复制,全部HCV RNA水平和蛋白水平降低,这种作用存在时间和剂量依赖性。Telaprevir处理HCV复制细胞,亲本Huh-7和HepG2细胞48小时后,对细胞没有毒性。

Determination of anti-HCV activity: Stable Huh-7 cells containing the self-replicating, subgenomic HCV replicon, which is identical in sequence to the I377neo/NS3-3'/wt replicon are used for anti-HCV assays. Replicon cells are incubated at 37 °C for the indicated period of time with Telaprevir serially diluted in DMEM plus 2% FBS and 0.5% dimethyl sulfoxide (DMSO). Total cellular RNA is extracted using an RNeasy-96 kit, and the copy number of HCV RNA is determined using a quantitative RTPCR (QRT-PCR) assay for the assessment of 50% inhibitory concentration (IC50

Cells are incubated with various concentrations of Telaprevir for 48 hours. Cell viability is determined by using a tetrazolium (MTS)-based cell viability assay.(Only for Reference)

402957-28-2

C36H53N7O6

679.85

特拉匹韦;LY-570310;Incivek;VX-950;MP-424

Ethanol:<1 mgml
DMSO:125 mg/mL (183.9 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years