Table 2. AXL inhibitors under development.
| Compound | Known Targets | Clinical Trials.gov identifier | Phase of Development | Sponsor | Functions in a disease indication and other preclinical research details | References |
|---|---|---|---|---|---|---|
| Small Molecule Inhibitors | ||||||
| LY2801653 | AXL, MET, MST1R | NCT01285037 | Phase 1 | Eli Lilly and Co. | An orally bioavailable multi-kinase inhibitor against MET, AXL, MST1R. | [120, 121] |
| MP-470 (Amuvatinib) | AXL, c-KIT, PDGFR, FLT3, RET, RAD51 |
NCT00894894 NCT00881166 NCT01357395 |
Phase 1 Phase 1 Phase 2 |
Astex Pharma. | c-Kit/AXL tyrosine kinase inhibitor investigated in stromal tumors and in breast cancer. | [102] |
| SKI-606 (Bosutinib) | AXL, Src Kinase, Abl, TGFB, BMP |
NCT00195260 NCT00319254 |
Phase 1 Phase 2 |
Pfizer | Treating HCC cells with Bosutinib decreased the AXL specific invasiveness of HCC cell lines. | [122] |
| MGCD 265 | AXL, MET, VEGFR |
NCT00697632 NCT00975767 |
Phase 1 and 2 Phase 1 |
Mirati Inc. | Phase 2 NSCLC | [123–126] |
| MGCD516 | MET, AXL, RET, TRK, DDR2, KDR, PDGFRA, or KIT | Preclinical | Mirati Inc. | Phase 1 planned | [139] | |
| ASP2215 | AXL, Flt3 | NCT02014558 | Phase 1 and 2 | Astellas Pharma. | A novel FLT3/AXL inhibitor: Preclinical evaluation in acute myeloid leukemia | [110] |
| XL184 (Cabozantinib) | AXL, c-MET, VEGFR-2, c-KIT, Flt 1/3/4, Tie2 and RET | NCT01639508 | Phase 2 and 3 | Exelixis | Medullary Thyroid cancer, Brain cancer, NSCLC and randomization discontinuation trial in various solid tumors | [127–130] |
| BMS-777607 (ASLAN 002) | AXL, Mer and MET | NCT01721148 | Phase 1 | Aslan Pharma. and Inventive Health Clinical | Selective small molecule kinase inhibitor against AXL, Mer, and Met. | [131] |
| GSK1363089/XL880 (Foretinib) | AXL, cMET, VEGFR2 | NCT02034097 | Phase 2 | GlaxoSmithKline | Restores lapatinib sensitivity in lapatinib-resistant breast cancer cells with AXL over expression. | [101] |
| SGI-7079 | AXL | NCT00409968 | Phase 2 | Astex Pharma | Decreased malignant properties in inflammatory breast cancer. Combination of SGI-7079 with erlotinib reversed erlotinib resistance in mesenchymal cell lines, xenograft model of mesenchymal NSCLC and patients. | [43, 93] |
| S49076 | AXL, MET, EGFR | ISRCTN00759419 | Phase 1 | Servier | Preclinical activity in colon carcinoma. | [132] |
| R428 (BGB324) | AXL | European Clinical trial | Phase Ia | BerGen BIO | Resensitized HN5-ER cells to erlotinib in head and neck cancer, reduced migration and invasion in melanomas, induced CLL B-cell apoptosis, reduced invasion and migration in EAC cell lines, reduced metastatic burden and extended survival in metastatic breast cancer. | [21, 133] |
| DP3975 | AXL | Preclinical | Deciphera Biotech | Inhibited cell migration and proliferation in mesotheliomas. | [140] | |
| NPS-1034 | AXL, MET | Preclinical | NeoPharma | Newly developed drug that targets both MET and AXL in NSCLC cells with acquired resistance to gefitinib or erlotinib. | [106] | |
| LDC1267 | AXL, Tyro, Mer | Preclinical | Induces NK cells to kill tumor cells in mouse metastatic breast cancer and melanoma model | [119] | ||
| NA80x1 | AXL | Preclinical | Inhibits AXL phosphorylation, cell motility, and invasion in MDA-MB-435 cells. | [141] | ||
| Receptor Monoclonal Antibody | ||||||
| YW327.6S2 | AXL | Preclinical | Anti-AXL monoclonal antibody. | [134] | ||
| Nucleotide Aptamer | ||||||
| GL21.T | AXL | Preclinical | Binds to the extracellular domain of AXL to inhibit its catalytic activity in lung cancer. | [135, 136] | ||