| Identification | Back Directory | [Name]
2H-1,4-Oxazino[3,2-c]quinolin-3(4H)-one, 9-[[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo[4,3-a]pyridin-3-yl]thio]-4-methyl- | [CAS]
1637658-98-0 | [Synonyms]
dalmelitinib
2H-1,4-Oxazino[3,2-c]quinolin-3(4H)-one, 9-[[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo[4,3-a]pyridin-3-yl]thio]-4-methyl- | [Molecular Formula]
C22H16FN7O2S | [MOL File]
1637658-98-0.mol | [Molecular Weight]
461.47 |
| Hazard Information | Back Directory | [Uses]
Dalmelitinib is an orally active selective c-Met kinase inhibitor (IC50: 2.9 nM) that binds to the ATP-binding region of c-Met. Dalmelitinib induces the phosphorylation of MET, partially or completely inhibits the phosphorylation of AKT and ERK. Dalmelitinib potently inhibits cancer cell (c-Met oncogene amplification) proliferation, and is used for the research of cancers like human non-small cell lung cancer (NSCLC)[1]. | [in vivo]
Dalmelitinib (Compound 4 d, intragastric administration, 10-60 mg/kg) significantly inhibits the tumor growth in a dose-dependent manner in MKN-45 tumor xenograft nude mice[1].
Dalmelitinib (intragastric administration, 5 mg/kg for a single dose) shows a high plasma concentration, longer half-life and mean residence time, low clearance rates in BALB/c small nude mice[1].
Dalmelitinib shows a high level of No Observed Adverse Effect Level (NOAEL) in mice long-term toxicity (225 mg/kg/day) and acute toxicity (600 mg/kg/day)[1].
| Animal Model: | MKN-45 tumor xenograft nude mice[1] | | Dosage: | 10, 30, 60 mg/kg | | Administration: | Intragastric administration | | Result: | Inhibited the tumor growth with the inhibitory rates of 29.5% (10 mg/kg), 34.2% (30 mg/kg), and 61.4% (60 mg/kg).
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| Animal Model: | BALB/c small nude mice (pharmacokinetic assay)[1] | | Dosage: | 5 mg/kg for a single dose | | Administration: | Intragastric administration | | Result: | Pharmacokinetic profile of Dalmelitinib (Compound 4 d)
| Compound | Cmax (ng/mL) | AUC (ng/mL/h) | t1/2 (h) | MRT (h) | CL/F (mL/min/kg) | Vz/F | | Dalmelitinib | 8628 | 122487 | 5.55 | 9.10 | 0.68 | 327 |
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| [References]
[1] Junjun Zhao, et al. Synthesis and biological evaluation of new [1,2,4]triazolo[4,3-a]pyridine derivatives as potential c-Met inhibitors. Bioorg Med Chem. 2016 Aug 15;24(16):3483-93. DOI:10.1016/j.bmc.2016.05.057 |
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