Table 5.
Nonspecific DDR inhibitors: specificities and clinical trials (adapted from ClinicalTrials.gov).
| Inhibitor | Targeted Kinases | In Vitro Assay (Cancer) | Preclinical (Cancer) |
Clinical (DDR Targeted) |
|---|---|---|---|---|
| Imatinib | BCR-ABL, DDR1, DDR2 | |||
| Nilotinib | ABL1, Kit, PDGFRA, PDGFRB, CSF1R, DDR1, DDR2 | DDR1: -Breast (decreased apoptosis and DDR1 phosphorylation) -Colon (increased proliferation, decreased DDR1 phosphorylation). |
-NCT02029001: Malignant solid neoplasms. Mutated DDR1, mutated DDR2. Phase 2 (recruiting). |
|
| Dasatinib | BCR-ABL, SRC kinase family, DDR1, DDR2 | DDR1: -Lung (decreased proliferation). -Gastric (decreased proliferation, migration, invasion). DDR2: -Head and neck (decreased proliferation, migration, invasion) |
DDR2: -Head and neck (zebrafish): decreased migration |
-NCT01491633: Squamous cell lung cancer. Mutated DDR2. Phase 2 (not evaluable, toxicity). -NCT04439305: lymphoma, myeloma, solid neoplasm. Mutated DDR2. Phase 2: withdrawn. -NCT01514864: NSCLC. Mutated DDR2. Phase 2: not completed, disease progression. |
| Sitravatinib (MGCD156) |
MET, AXL, VEGFR1, VEGFR2, VEGFR3, PDGFRA, PDGFRB, TRKA, TRKB, DDR2 | -NCT02219711: NSCLC, renal cell carcinoma. Mutated DDR2. Phase 1 (recruiting). |