Table 4.
CalcuSyn analysis of PSI-352938 combination studies with ITMN-191, ACH-806, BMS-790052, a benzothiadiazine NNI, PSI-6130, or PSI-7851
Combination and ratioa | Combination indexb |
rd | ||
---|---|---|---|---|
EC50 | EC75 | EC90 | ||
PSI-352938 and ITMN-191 | ||||
20:1 | 0.64 | 0.68 | 0.73 | 0.97 |
40:1 | 0.72 | 0.73 | 0.74 | 0.96 |
80:1 | 0.93 | 0.83 | 0.73 | 0.99 |
160:1 | 1.13 | 1.12 | 1.10 | 0.98 |
PSI-352938 and ACH-806 | ||||
1:5 | 0.67 | 0.68 | 0.69 | 0.97 |
1:2.5 | 0.63 | 0.64 | 0.66 | 0.95 |
1:1.25 | 0.78 | 0.76 | 0.73 | 0.98 |
1:0.63 | 0.76 | 0.76 | 0.76 | 0.99 |
PSI-352938 and BMS-790052 | ||||
12,500:1 | 1.01 | 0.92 | 0.85 | 0.97 |
25,000:1 | 1.09 | 1.11 | 1.14 | 0.98 |
50,000:1 | 0.91 | 0.89 | 0.88 | 0.93 |
100,000:1 | 0.92 | 0.9 | 0.88 | 0.93 |
PSI-352938 and NNIc | ||||
0.8:1 | 0.60 | 0.61 | 0.63 | 0.99 |
1.6:1 | 0.80 | 0.70 | 0.62 | 0.95 |
3.2:1 | 0.70 | 0.63 | 0.58 | 0.99 |
6.4:1 | 0.77 | 0.77 | 0.78 | 0.92 |
PSI-352938 and PSI-6130 | ||||
1:20 | 0.51 | 0.6 | 0.71 | 0.94 |
1:10 | 0.51 | 0.63 | 0.78 | 0.98 |
1:5 | 0.62 | 0.66 | 0.71 | 0.98 |
1:2.5 | 0.58 | 0.62 | 0.66 | 0.93 |
PSI-352938 and PSI-7851 | ||||
1:1.25 | 0.80 | 0.76 | 0.71 | 0.99 |
1:0.63 | 1.06 | 1.03 | 1.00 | 0.98 |
1:0.31 | 1.02 | 0.91 | 0.81 | 0.99 |
1:0.16 | 1.17 | 1.15 | 1.13 | 0.98 |
Compounds were combined in a checkerboard format, where 10 different concentrations of PSI-352938 were added horizontally and 8 different concentrations of another HCV inhibitor were added vertically to a 96-well plate. For each ratio indicated, at least six different combinations of PSI-352938 and the other anti-HCV compound were included for calculation of the combination index value.
Combination index values at 50%, 75%, and 90% inhibition were calculated using the CalcuSyn program.
The NS5B NNI used here was a benzothiadiazine-derived compound targeting an allosteric site within the palm domain of NS5B.
The r value is the linear correlation coefficient that indicates the goodness of fit for the data.