1.
HGF/c-Met通路抑制剂, 抑制机制及应用情况
HGF/c-Met pathway Inhibitors developed for lung cancer and the other solid tumors
| Compound | Company | Mechanism of action | Phase/Type of tumor | Ref |
| NCT References are available on http://clinicaltrials.gov/ct2/home; NSCLC:non-small cell lung cancer; DLBCL:diffuse large B cell lymphoma; TKI:tyrosine kinase inhibitors; VEGF:vascular endothelial growth factor; HGF:hepatocyte growth factor. | ||||
| Antagonists | ||||
| NK2/NK4 | Inhibit HGF binding to Met | Preclinical/Solid tumors | [41, 55] | |
| Uncleaved HGF | Inhibit HGF activation | Preclinical/Solid tumors | [56] | |
| Decoy MET | Compugen | Inhibit MET activationr | Preclinical/NSCLC | [57] |
| Antibodies | ||||
| Rilotumumab | Amgen | Anti-HGF (IgG2) | Phase Ⅰ-Ⅱ/NSCLC | NCT01233687 |
| Ficlatuzumab | AVEO | Anti-HGF (IgG1) | Phase Ⅰb-Ⅱ/NSCLC | NCT01039948 |
| TAK-701 | Millennium | Anti-HGF (IgG1) | Phase Ⅰ/Solid Tumors | NCT00831896 |
| Onartuzumab | Genentech | Anti-Met (IgG1) | Phase Ⅲ/ NSCLC | NCT01456325 |
| OA-5D5 | Genentech | Anti-Met | Preclinical/ NSCLC | [58] |
| DN30 | Metheresis | Anti-Met | Preclinical/ GTL16 | [59] |
| CE-355621 | Pfizer | Anti-Met | Preclinical/ U87-MG | [60] |
| Small-molecule c-Met inhibitors | ||||
| Tivantinib | ArQule | Selective, Met TKI (Non-ATP) | Phase Ⅲ/NSCLC | NCT01377376 |
| AMG337 | Amgen | Selective, Met TKI (ATP) | Phase Ⅰ/Solid tumors | NCT01253707 |
| SGX523 | SGX Pharma. | Selective, Met TKI (ATP) | Phase Ⅰ /Solid tumors | NCT00606879 |
| AMG 208 | Amgen | Selective, Met TKI | Phase Ⅱ/DLBCL | NCT01740792 |
| PF-04217903 | Pfizer | Selective, Met TKI (ATP) | Phase Ⅰ/Solid tumors | NCT00706355 |
| EMD 1214063 | EMD Serono | Selective, Met TKI | Phase Ⅰ/Solid tumors | NCT01014936 |
| BMS777607 | Bristol-Myers Squibb | Selective, Met TKI (ATP) | Phase Ⅰ-Ⅱ/Solid tumors | NCT00605618 |
| JNJ38877605 | Johnson & Johnson | Selective, Met TKI | Phase Ⅰ/Solid tumors | NCT00651365 |
| INCB28060 | Incyte& Novartis | Selective, Met TKI (ATP) | Phase Ⅰ/Advanced cancer | NCT01072266 |
| PHA665752 | Tocris Bioscience | Selective, Met TKI (ATP) | Preclinical/NSCLC | [61] |
| Crizotinib | Pfizer | Selective, Met TKI (ATP) | Phase Ⅲ/ALK-altered NSCLC Ph Ⅰ-Ⅱ/ solid tumors |
NCT01639001 |
| Golvatinib | Eisai | TKI of c-Met and VEGFR | Phase Ⅰ-Ⅱ/Solid tumors | NCT01433991 |
| Cabozantinib | Exelixis | Receptor TKI (ATP) | Phase Ⅱ/NSCLC Ph Ⅲ/ solid tumors |
NCT01708954 NCT01908426 |
| Foretinib | Exelixis | Receptor TKI (ATP) | Phase Ⅰ-Ⅱ/Solid tumors | NCT01068587 |
| MGCD265 | MethylGene | TKI of Met and VEGF | Phase Ⅱ/NSCLC | NCT00975767 |