For research use only. Not for therapeutic Use.
AMG-208 (Cat.No:I000077) is a potent and selective small molecule inhibitor of c-Met receptor tyrosine kinase. It binds to the inactive conformation of c-Met and inhibits its phosphorylation and activation, thereby blocking downstream signaling pathways. AMG-208 has shown promising preclinical results in various cancer models and is being developed as a potential therapeutic agent for cancer.
| Catalog Number | I000077 |
| CAS Number | 1002304-34-8 |
| Synonyms | 7-methoxy-4-[(6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy]quinoline |
| Molecular Formula | C₂₂H₁₇N₅O₂ |
| Purity | ≥95% |
| Target | Metabolic Enzyme/Protease |
| Solubility | DMSO: ＜ 1 mg/mL, H2O: ＜ 1 mg/mL, Ethanol: ＜ 1 mg/mL |
| Storage | 3 years -20℃ powder |
| IC50 | 9.3 nM |
| IUPAC Name | 7-methoxy-4-[(6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy]quinoline |
| InChI | InChI=1S/C22H17N5O2/c1-28-16-7-8-17-19(13-16)23-12-11-20(17)29-14-22-25-24-21-10-9-18(26-27(21)22)15-5-3-2-4-6-15/h2-13H,14H2,1H3 |
| InChIKey | HEAIZQNMNCHNFD-UHFFFAOYSA-N |
| SMILES | COC1=CC2=NC=CC(=C2C=C1)OCC3=NN=C4N3N=C(C=C4)C5=CC=CC=C5 |
| Reference | 1:Oncotarget. 2015 Jul 30;6(21):18693-706. A first-in-human study of AMG 208, an oral MET inhibitor, in adult patients with advanced solid tumors.Hong DS,Rosen P,Lockhart AC,Fu S,Janku F,Kurzrock R,Khan R,Amore B,Caudillo I,Deng H,Hwang YC,Loberg R,Ngarmchamnanrith G,Beaupre DM,Lee P, PMID: 26155941 PMCID: PMC4621921 DOI: 10.18632/oncotarget.4472 </br><span>Abstract:</span> BACKGROUND: This first-in-human study evaluated AMG 208, a small-molecule MET inhibitor, in patients with advanced solid tumors.METHODS: Three to nine patients were enrolled into one of seven AMG 208 dose cohorts (25, 50, 100, 150, 200, 300, and 400 mg). Patients received AMG 208 orally on days 1 and days 4-28 once daily. The primary objectives were to evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of AMG 208.RESULTS: Fifty-four patients were enrolled. Six dose-limiting toxicities were observed: grade 3 increased aspartate aminotransferase (200 mg), grade 3 thrombocytopenia (200 mg), grade 4 acute myocardial infarction (300 mg), grade 3 prolonged QT (300 mg), and two cases of grade 3 hypertension (400 mg). The MTD was not reached. The most frequent grade ≥3 treatment-related adverse event was anemia (n = 3) followed by hypertension, prolonged QT, and thrombocytopenia (two patients each). AMG 208 exposure increased linearly with dose; mean plasma half-life estimates were 21.4-68.7 hours. One complete response (prostate cancer) and three partial responses (two in prostate cancer, one in kidney cancer) were observed.CONCLUSIONS: In this study, AMG 208 had manageable toxicities and showed evidence of antitumor activity, particularly in prostate cancer.TRIAL REGISTRATION: ClinicalTrials.gov NCT00813384. |
