Table 1.
Thermodynamic and kinetic parameters for inhibition of cathepsin L by CLIK-148, CLIK-181 and 1-4a
Compound | Ki (⍰M) | kinact (s−1) | kinact/Ki (M−1 s−1) |
---|---|---|---|
CLIK-148 | 1.4 ± 0.7 | 0.015 ± 0.005 | 11000 ± 3000 |
CLIK-181 | 1.3 ± 0.1 | 0.020 ± 0.003 | 15000 ± 2000 |
1 | 0.77 ± 0.27 | 0.011 ± 0.005 | 13000 ± 2800 |
2 | 1.6 ± 0.2 | 0.015 ± 0.001 | 9400 ± 1000 |
3 (dark) | 1.0 ± 0.2 | 0.016 ± 0.002 | 15000 ± 2000 |
4 (dark) | 14 ± 4 | 0.008 ± 0.002 | 570 ± 60 |
Inhibition data were acquired using cathepsin L (4 nM), Z-Phe-Arg-AMC (10 μM), and inhibitor (0.1–2.5 μM) in 0.4 M acetate buffer, pH 5.5, <1% DMSO, 4 mM EDTA, 0.01% Triton X-100, DTT = 8 at 25 °C. Data are averages of 3 independent experiments with errors equal to standard deviations. Data for 3 and 4 were collected under dark conditions. See SI for more details.