Table 2.
Kinetic properties and IC50 values of CB-5083 and NMS-873 for p97 and the P472L mutant with D1 or D2 Walker motif mutations
Values shown are mean ± S.E. (n = 4).
| KM | kcat | kcat/KM | CB-5083 | NMS-873 | |
|---|---|---|---|---|---|
| μm | min−1 | μm−1 min−1 × 10−3 | nm | nm | |
| WT | 91 ± 25 | 11.4 ± 0.9 | 125 ± 35 | 5 ± 0.5 | 14 ± 1 |
| D1 K251A | 43 ± 5 | 0.27 ± 0.01 | 6.2 ± 0.7 | 43 ± 6 | 32 ± 4 |
| D1 E305Q | 66 ± 8 | 12.0 ± 0.4 | 187 ± 23 | 10 ± 1 | 16 ± 2 |
| D2 K524A | 115 ± 14 | 0.25 ± 0.01 | 2.2 ± 0.3 | NDa | ND |
| D2 E578Q | 37 ± 4 | 2.37 ± 0.07 | 64 ± 7 | 20 ± 5 | 513 ± 101 |
| P472L | 48 ± 6 | 49 ± 2 | 1009 ± 119 | 138 ± 16 | 569 ± 54 |
| D1 K251A | 41 ± 5 | 19 ± 0.6 | 460 ± 55 | 29 ± 4 | 1837 ± 389 |
| D1 E305Q | 38 ± 5 | 29 ± 1 | 752 ± 109 | 48 ± 6 | 4299 ± 1433 |
| D2 K524A | 331 ± 43 | 0.68 ± 0.04 | 2.0 ± 0.3 | ND | ND |
| D2 E578Q | 22 ± 4 | 1.64 ± 0.06 | 73 ± 12 | 53 ± 10 | >10,000b |
a ND means not determined.
b Activity inhibition was not observed over the concentration range tested.