Effects of resistance mutations on the inhibitory activity of compounds 1–8.

The IC50 values of the compounds were determined in the cleavage assays in vitro using the recombinant wild-type (WT) and mutant (V36M, R155K, A156T, D168A and V170A) NS3/4A constructs and Ac-DE-D(Edans)-EE-Abu-ψ-[COO]AS-K(Dabcyl)-NH2 as a substrate.¥The IC50 was directly measured in vitro using the purified recombinant WT and mutant NS3/4A constructs [75].*The IC50 was measured using the mutant HCV replicon with luciferase readout [9], [14], [15]. FC, the fold change in the IC50 for the mutant compared to that the WT proteinase. ND, not determined, n/a, not applicable.

本研究通过体外切割实验，采用重组野生型（WT）及突变型（V36M、R155K、A156T、D168A与V170A）NS3/4A蛋白构建体，以Ac-DE-D(Edans)-EE-Abu-ψ-[COO]AS-K(Dabcyl)-NH2为底物，测定了各化合物的半数抑制浓度（IC50）。利用纯化的重组野生型及突变型NS3/4A蛋白构建体，可直接在体外完成IC50的测定[75]。另有研究采用搭载荧光素酶读数系统的突变型丙型肝炎病毒（HCV）复制子完成了IC50的测定[9],[14],[15]。FC指突变体相较于野生型蛋白酶的IC50倍数变化；ND表示未测定，n/a表示不适用。