Table 2.
Biophysical and biochemical evaluation of WT and mutant MET proteins
| MET (1051–1349) protein variants | Tepotinib |
|||
|---|---|---|---|---|
| TSA |
nDSF |
Biochemical IC50 (nM) | ||
| Tm (°C) | ΔTm (°C)a | ΔTm (°C)a | ||
| WT (no ATP preincubation) | 47 | +15 | +18.6 | 1.7 |
| WT (after ATP preincubation) | 47 | +10 | +13.5 | NT |
| Y1234E/Y1235E | 47 | +10 | +13.9 | NT |
| Y1235D | 48 | +11 | +14 | 1.7 |
| F1200I | 53 | +9 | +9.9 | 232 |
| L1195V | 49 | +4/10b | +8.5/13.4c | 300 |
| Y1230C | 48 | +1 | +4.3 | 3900 |
NT, not tested; TSA, thermal shift assay.
a
Tm shifts calculated based on main transition.
b
Two transitions observed in TSA.
c
Two transitions observed in nDSF based on two different Tm values for the apo protein.