Table 5. Selectivity of Selected BTK Inhibitors over Kinases with a Reactive Cysteine at the 481 Position.
compound |
|||||||
---|---|---|---|---|---|---|---|
amino acid @484 position | tolebrutinib (2) Kd [nM] | evobrutinib (4) Kd [nM] | 10Kd [nM] | 25Kd [nM] | 27Kd [nM] | ||
BTK Kd [nM] | Asn | 1.4 | 4.6 | 0.6 | 0.63 | 0.31 | |
Kinase with Cys481 | Fold Selectivity for BTK (off-target kinase Kd/BTK Kd) | ||||||
BMX | Asn | 3 | 4 | 43 | 43 | 14 | |
TEC | Asn | 1 | <1 | 9 | 9 | 7 | |
TXK | Asn | 5 | 37 | 27 | 27 | 6 | |
JAK3 | Asp | 847 | 1217 | 157 | 157 | 390 | |
BLK | Asp | 3 | 133 | 460 | 460 | 839 | |
ITK | Asp | 671 | 587 | 1200 | 1206 | 274 | |
EGFR | Asp | 9 | 2000 | >10 000 | >10 000 | 9355 | |
ERBB2 | Asp | 2 | 1152 | >10 000 | >10 000 | 7419 | |
ERBB4 | Glu | 4 | 137 | 700 | 714 | 7741 |