| Identification | Back Directory | [Name]
1,6-Naphthyridin-4(1H)-one, 5-[[3-fluoro-4-[[7-(2-hydroxy-2-methylpropoxy)-4-quinolinyl]oxy]phenyl]amino]-3-phenyl- | [CAS]
2101241-90-9 | [Synonyms]
met-kinase-in-2
1,6-Naphthyridin-4(1H)-one, 5-[[3-fluoro-4-[[7-(2-hydroxy-2-methylpropoxy)-4-quinolinyl]oxy]phenyl]amino]-3-phenyl- | [Molecular Formula]
C33H27FN4O4 | [MOL File]
2101241-90-9.mol | [Molecular Weight]
562.59 |
| Chemical Properties | Back Directory | [Boiling point ]
714.6±60.0 °C(Predicted) | [density ]
1.349±0.06 g/cm3(Predicted) | [storage temp. ]
4°C, protect from light, stored under nitrogen | [solubility ]
DMSO : 100 mg/mL (177.75 mM; Need ultrasonic) | [form ]
Solid | [pka]
14.23±0.29(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
MET kinase-IN-2 is a potent, selective, orally bioavailable MET kinase inhibitor with an IC50 of 7.4 nM. MET kinase-IN-2 has antitumor activity[1]. | [in vivo]
MET kinase-IN-2 (3-37.5 mg/kg; p.o.; 7 days per week for 3 weeks) exhibits statistically significant tumor growth inhibition in the U-87 MG 24 xeograft model[1].
MET kinase-IN-2 treatment shows that the Cmax, AUC0-∞, T1/2，CL, and F% values are 1.5 μg/mL, 10.7 μg?h/mL, 4.9 hours, 0.5 L/h/kg, and F=32%, respectively[1]. | Animal Model: | 4-6 weeks old Female nude mice (U-87 MG xenograft model)[1] | | Dosage: | 3, 6, 12.5, 37.5 mg/kg | | Administration: | P.o.; 7 days per week for 3 weeks | | Result: | Induced dose-dependent tumor growth inhibition.
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| Animal Model: | Male SD rats[1] | | Dosage: | 5 mg/kg | | Administration: | P.o. (Pharmacokinetic Analysis) | | Result: | Displayed favorable overall PK profiles, with maximal plasma concentration (Cmax=1.5 μg/mL, 5-fold higher to that of IV), plasma exposure (AUC0-∞=10.7 μg?h/mL, 9.7-fold higher to that of IV), half-life (T1/2=4.9 h, 4.9-fold longer to that of IV), total clearance CL (0.5 L/h/kg; 10-fold lower to that of IV), and oral bioavailability (F=32%, 2.7-fold higher to that of IV) after oral dose of 5 mg/kg (10 mg/kg for IV).
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| [References]
[1] Chen T, et al. Discovery of 1,6-naphthyridinone-based MET kinase inhibitor bearing quinoline moiety as promising antitumor drug candidate. Eur J Med Chem. 2020;192:112174. DOI:10.1016/j.ejmech.2020.112174 |
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