Table 1.
Chemical structure | Name(s) (Brand name) | Target(s) | Examples of resistance- conferring mutationsRef | Mode of Action |
---|---|---|---|---|
Crizotinib (Xalkori™) | ALK | ALK-L1196M, C1156Y14,17,19 | ATP-competitive | |
Ceritinib (Zykadia™) | ALK | ALK-L1198F19,20 | ATP-competitive | |
Lorlatinib (Lorbrena™) | ALK | ALK-C1156-L1198F19,20 | ATP-competitive | |
Imatinib (Gleevec™) | BCR-ABL | BCR-ABL-T315I3,16 | ATP-competitive | |
Dasatinib (Sprycel™) | BCR-ABL | BCR-ABL-T315I3,16 | ATP-competitive | |
Vandetanib (Caprelsa™) | BCR-ABL-V299L | BCR-ABL-V299L-E255K, V299L-F317L78 | ATP-competitive | |
EGFR | ||||
ABL001 Asciminib | BCR-ABL-WT | BCR-ABL-A337C, P465S, V468F40 | allosteric | |
BCR-ABL-T315I | ||||
LOXO-195 | TrkA, B, C | N/A | ATP-competitive | |
Larotrectinib LOXO-101 (Vitrakvi™) | TrkA, B, C | TrkA-F589L, G595R, G667C24,25 | ATP-competitive | |
TrkC-G623R, G696A24,25 | ||||
Osimertinib (Tagrisso™) | EGFR-T790M | EGFR-C797S, L718Q35 | covalent | |
WZ4020 | EGFR-T790M | EGFR-C797S35 | covalent | |
Indisulam | RBM39 | RBM39-G268V,W,R,E67 | “molecular glue” | |
DCAF15 | ||||
Thalidomide | CRBN | IKFZ1-Q146H64,65 | “molecular glue” | |
IKFZ1 | IKFZ3-Q147H64,65 | |||
IKFZ3 | CRBN-W386A64,65 | |||
CRBN-W400A64,65 | ||||
MT-802 | CRBN | N/A | PROTAC | |
BTK(C481S) |