Table 2.
Characteristics of second-generation ALK inhibitors.
| Drugs | Molecular targets other than ALK | Activity against L1196M | Activity against C1156Y | Activity against G1202R | Activity against other crizotinib-resistant mutations | No activity | Mechanism of acquired resistance |
|---|---|---|---|---|---|---|---|
| Ceritinib | IGF1-R, InsR, STK22D | Yes | No | No | G1269A, S1206Y, I1171T, V1180L | 1151T-ins, L1152P, F1174C | F1174C, G1202R |
| Alectinib | GAK, LTK | Yes | Yes | No | G1269A, S1206Y, L1152R, F1174L, 1151T-ins | F1174V | I1171T, V1180L, G1202R |
| AP26113 | ROS1, EGFRdel19/T790M | Yes | Yes | Yes | G1269A, S1206Y, D1203N, F1174C, 1151T-ins, G1269S, I1171T, E1210K, F1245C, S1206R* | NA | NA |
| ASP3026 | ROS1, ACK | Yes | NA | NA | NA | NA | NA |
| PF-06463922 | ROS1 | Yes | NA | Yes | G1269A | NA | NA |
| TSR-011 | TRK-A, TRK-B, TRK-C | Yes | NA | NA | NA | NA | NA |
| RXDX-101 | ROS1, TRK-A, TRK-B, TRK-C | Yes | Yes | NA | NA | NA | NA |
| X-396 | MET | Yes | Yes | NA | NA | NA | NA |
| CEP-37440 | FAK | NA | NA | NA | NA | NA | NA |
*
S1206R confers to greatest resistance to AP26113 among the tested crizotinib-resistant mutations.
ALK, anaplastic lymphoma kinase; NA, not available.