Table 1 ABL kinase inhibitors
From: Role of the ABL tyrosine kinases in the epithelial–mesenchymal transition and the metastatic cascade
Name | Alternative name | Inhibitor type | Targets | References describing inhibitor targets | Clinical trials in solid tumors | Regulatory status |
|---|---|---|---|---|---|---|
Imatinib | Gleevec/STI57 | ATP-site, Type II | ABL1, ABL2, BCR-ABL1, CSF1R, DDR1, DDR2, KIT, NQO2, PDGFR1 | [160] | Yes Non-small cell lung cancer: NCT01011075; NCT00408460 Breast Cancer: NCT00193180; NCT00338728; NCT00087152 Gastrointestinal tumors: NCT01151852; NCT00867113 Melanoma: NCT00424515; NCT00470470 | FDA approved for CML, Ph + ALL, MDS/MPD, ASM, HES/CEL, DFSP, GIST |
Dasatinib | Sprycel/ BMS-354825 | ATP-competitive, Type I | ABL1, ABL2, BCR-ABL1, BLK, BTK, CSK, CSR1R, DDR1, DDR2, EGFR, ERBB2, FGR, FRK, FYN, GAK, GCK, HCK, ILK, KIT, LCK, LIMK1, LIMK2, LYN, MAP2K, MAP3K, MAP4K, PDGFR, RIPK2, SLK, SRC, SYK, TEC, TYK2, YES1, | [160–162] | Yes Non-small cell lung cancer: NCT00858403; NCT00826449; NCT01999985 Breast Cancer: NCT00817531,NCT00924352, NCT00767520, NCT00410813 Gastrointestinal tumors: NCT00568750; NCT01643278;NCT00504153 Melanoma: NCT00597038;NCT00436605 | FDA approved for CML, Ph + ALL |
Nilotinib | Tasigna/AMN107 | ATP-site, Type II | ABL1, ABL2, BCR-ABL1, CSF1R, DDR1, DDR2, KIT, NQO2, PDGFR | [160] | Yes Breast Cancer: NCT04205903 Gastrointestinal tumors: NCT00976612; NCT00471328 Melanoma: NCT01395121; NCT00788775; NCT01099514 | FDA approved for CML |
Bosutinib | Bosulif/SKI-606 | ATP-competitive, Type I | ABL1, ABL2, BCR-ABL1, CAMK2G, CDK2, HCK, LYN, MAPKK1, MAPKK2, MAPKKK2, SRC | [163–165] | Yes Non-small cell lung cancer: NCT03023319 Breast Cancer: NCT00793546; NCT00319254; NCT00880009; NCT03854903; NCT00959946; NCT00759837 Advanced Solid Tumors: NCT03297606; NCT01001936 | FDA approved for CML, Ph + CML |
Ponatinib | Iclusing/AP24534 | ATP-site, Type II | ABL1, ABL2, BCR-ABL1, BLK, CSFR1, DDR1, DDR2, EPHRs, FGFR1, FGFR2, FGR, FLT3, FRK, FYN, HCK, LCK, LYN, RET, SRC, TEK, TIE2, TRKA, TRKB, TRKC, PDGFR, VEGFR1, VEGFR2, VEGFR3, YES1 | [166–169] | Yes Non-small cell lung cancer: NCT01761747; NCT03704688; NCT01935336; NCT01813734; NCT01813734; Breast Cancer: NCT03878524; NCT04591431 Gastrointestinal tumors: NCT01874665 | FDA approved for CML, Ph + ALL |
Axitinib | Inlyta/AG013736 | ATP-competitive, Type I | BCR-ABL1 (T315I), KIT, PDGFR, VEGFR1, VEGFR2, VEGFR3 | [170] | Yes Non-small cell lung cancer: NCT03472560; NCT00094094; NCT00094094 Breast Cancer: NCT00076024; Gastrointestinal tumors: NCT00700258 Renal Cell Carcinoma: NCT02493751; NCT00678392; NCT00920816; NCT02579811 | FDA approved for Renal Cell Carcinoma |
Vandetanib | Caprelsa/ZD-6474 | ATP-competitive, Type I | ABL1, EGFR, RET, VEGFR | [171] | Yes Non-small cell lung cancer: NCT01586624; NCT00753714; NCT01823068 Breast Cancer: NCT01934335; NCT00481845; NCT00494481 Gastrointestinal tumors: NCT02015065 Thyroid Cancer: NCT01876784; NCT01496313; | FDA approved for Advanced Medullary Thyroid Cancer |
GNF2, GNF5 | Allosteric | ABL1, ABL2, BCR-ABL1 | [147] | No | Not FDA approved | |
ABL001 | Asciminib | Allosteric | ABL1, ABL2, BCR-ABL1 | [148] | Yes- Advanced solid tumors: NCT04492033; NCT03292783 | Phase III Clinical Trials in CML |
DAS‐6‐2‐2‐6‐CRBN | PROTAC | BCR-ABL1 | [155] | No | Preclinical Studies Only | |
BOS‐6‐2‐2–6‐CRBN | PROTAC | BCR-ABL1 | [155] | No | Preclinical Studies Only | |
GMB-475 | PROTAC | BCR-ABL1 | [154] | No | Preclinical Studies only |