Table 2.
Type I kinase inhibitors against Axl.
| Inhibitor/Developer | Target(s) | IC50 for Axl | Indications Approved by the FDA | ||||
|---|---|---|---|---|---|---|---|
| Crizotinib (PF-02341066) Pfizer |
Axl, Alk, c-Met, Ron |
in vitro: 294 nM |
Approved for patients with ALK- or ROS1-positive NSCLC and pediatric ALK-positive anaplastic large-cell lymphoma | ||||
| Bosutinib (SKI-606) Pfizer |
Axl, Src kinases, Abl, TGF, BMP | in vitro: 0.56 μM cells: 1.65 μM |
Approved for patients with chronic, accelerated, or blast phase Philadelphia chromosome chronic myelogenous leukemia | ||||
| Sunitinib (SU11248) Pfizer |
Axl, Kit, Flt3, PDGFR, VEGFR2 | in vitro: 9 nM | Approved for renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor and metastatic pancreatic neuroendocrine tumors | ||||
| Inhibitor/Developer | Target(s) | IC50 for Axl | Clinical Trial # | Phase | Strategy | Status | Indications |
| Bemcentinib (BGB324, R428) Rigel Pharmaceuticals/BerGen BIO |
Axl | in vitro: 14 nM cells: <30 nM |
NCT03965494 | I | Monotherapy | Recruiting | Glioblastoma |
| NCT02922777 | I | Combination | Recruiting | NSCLC | |||
| NCT03649321 | I/II | Combination | Recruiting | Pancreatic adenocarcinoma | |||
| NCT02872259 | I/II | Combination | Recruiting | Melanoma | |||
| NCT03824080 | II | Monotherapy | Active, not recruiting | Acute myeloid leukemia (AML), Myelodysplastic syndrome | |||
| NCT03654833 | II | Combination | Recruiting | Mesothelioma | |||
| NCT03184558 | II | Combination | Completed | TNBC, TN-inflammatory breast cancer | |||
| NCT03184571 | II | Combination | Recruiting | NSCLC | |||
| Amuvatinib (MP-470) Astex Pharmaceuticals |
c-Kit, Axl, c-Met, PDGFRα, FLT3, c-Ret, RAD51 | cells: <1 μM | NCT00881166 | I | Combination | Completed | Invasive malignancy except non-melanoma skin cancers or cervical carcinoma in situ |
| NCT00894894 | I | Monotherapy | Completed | Unresectable or metastatic solid tumor | |||
| NCT01357395 | II | Monotherapy | Completed | Small-cell lung cancer (SCLC) | |||
| Dubermatinib (TP-0903) Tolero Pharmaceuticals |
Axl, Aurora A and B, JAK2, Alk, Abl, Mer | in vitro: 27 nM cells: 222 nM |
NCT02729298 | I | Monotherapy | Active, not recruiting | Advanced metastatic or progressive solid tumor (Phase 1b: EGFR positive NSCLC; BRAF-, KRAS-, or NRAS-mutated colorectal carcinoma; recurrent ovarian carcinoma; BRAF-mutated melanoma) |
| NCT03013998 | I/II | Monotherapy/ Combination |
Recruiting | AML | |||
| NCT04518345 | I/II | Monotherapy | Recruiting | AML | |||
| NCT03572634 | I/II | Combination | Terminated | Chronic lymphocytic leukemia, small lymphocytic lymphoma | |||
| S49076 Servier |
Met mutants, Axl, Mer, FGFRs | in vitro: 7 nM cells: 56 nM |
ISRCTN00759419 | I | Monotherapy | Completed | Advanced solid tumors |
| ISRCTN11619481 | I/II | Combination | Completed | GBM | |||
| SNS-314 Sunesis Pharmaceuticals |
Aurora-A, -B, -C, Trk A/B, Flt4, Axl, c-Raf | in vitro: 84 nM |
NCT00519662 | I | Monotherapy | Completed | Advanced solid tumors |
| NA80x1 Wyeth-Ayerst Research/ Max Planck Institute of Biochemistry |
Axl | in vitro: 12.8 μM cells: 4.11 μM |
Preclinical | - | Monotherapy | - | - |
| SGI-7079 Northwestern University |
Axl, Met, Mer, Yes, Ret, Flt3 | in vitro: 58 nM cells: <1 μM |
Preclinical | - | Monotherapy/ Combination |
- | - |
| DP-3975 Deciphera Pharamaceuticals |
Axl | cells: 0.1 μM | Preclinical | - | Monotherapy | - | - |
| UNC569 University of North Carolina |
Mer, Tyro3, Axl | in vitro: 37 nM |
Preclinical | - | Monotherapy | - | - |
| UNC2025 University of North Carolina |
Mer, Flt3, Axl, Tyro3 | in vitro: 1.6 nM |
Preclinical | - | Monotherapy | - | - |
Bold: preferred target.