Table 5.
Examples of drugs with TRK inhibitory activity
| IC50 (nM) | Target other than TRK (IC50 < 500 nM) |
|||
|---|---|---|---|---|
| TRKA | TRKB | TRKC | ||
| Entrectinib | 2 | 0.1 | 0.1 | ALK, ROS1 |
| Larotrectinib | 9 | 4 | 4 | — |
| Cabozantinib | NA | 7 | NA | ALK, AXL, BLK, BTK, EPHA4, EPHB4, FAK, FLT1, FLT3, FLT4, FYN, KDR, KIT, LYN, MAP2K1, MET, PDGFRB, RAF1, RET, RON SAPK4, TIE2, YES |
| Crizotinib | 1 | 1 | NA | ABL, ALK, ARG, AXL, FES, LCK, LYN, MER, MET, RON, ROS1, SKY, TIE2, YES |
| Altiratinib | 0.9 | 4.6 | 0.8 | MET, TIE2 VEGFR2 |
| Belizatinib | < 3 | < 3 | < 3 | ALK |
| BMS-754807 | 7 | 4 | NA | AURKA, AURKB, FLT3, IGF1R, INSR, MET, RON |
| Danusertib | 31 | NA | NA | ABL, AURKA, AURKB, AURKC, FGFR1, RET |
| DS-6051b | < 2 | < 2 | < 2 | ALK, ROS1 |
| LOXO-195 | 4 | 2 | 1 | — |
| Merestinib | 15–320 | 15–320 | 15–320 | AXL, DDR1, DDR2, FLT3, MET, MERTK, MKNK1, MKNK2, MST1R, ROS1, TEK |
| MK-5108 | 2 | 13 | NA | ABL, AURKA, AURKB, AURKC, AXL, BRK, EPHA1, EPHA2, FLT1, FLT4, GSK3A, JNK3, KDR, LOK, MER, PTK5, ROS, TIE2, YES |
| PLX-7486 | < 10 | < 10 | < 10 | AURKA, AURKB, CSF1R, MAP3K2, MAP3K3 |
| Sitravatinib | 5 | 9 | NA | RET, CBL, CHR4q12, DDR, AXL, DDR1, DDR2, EPHA2, EPHA3, EPHA4, EPHB2, EPHB4, FLT1, FLT3, FLT4, KDR, KIT, MER, MET, PDGFRA, RET, RON, ROS, SRC |