| Identification | Back Directory | [Name]
Propanimidamide, N-[[(4-chlorophenyl)methyl]sulfonyl]-N'-[3-fluoro-4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl]oxy]phenyl]-3-methoxy- | [CAS]
2443380-34-3 | [Synonyms]
c-Met-IN-14
Propanimidamide, N-[[(4-chlorophenyl)methyl]sulfonyl]-N'-[3-fluoro-4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl]oxy]phenyl]-3-methoxy- | [Molecular Formula]
C34H38ClFN4O7S | [MOL File]
2443380-34-3.mol | [Molecular Weight]
701.2 |
| Hazard Information | Back Directory | [Uses]
c-Met-IN-14 (compound 26af) is a selective inhibitor of c-Met kinase from N-sulfonylamidine-based derivatives, with an IC50 value of 2.89 nM. c-Met-IN-14 shows anticancer activity by blocking phosphorylation of c-Met, and arrests cell cycle at G2/M phase. c-Met-IN-14 induces apoptosis of A549 cells in a dose-dependent manner[1]. | [in vivo]
c-Met-IN-14 (compound 26af) (p.o.; 8 mg/kg) exhibits safety profile and favorable pharmacokinetic properties in BALB/c mouse, with rapid absorption (Tmax=2.5 h), high maximum concentration (Cmax=1228.4 ng/mL), high plasma exposure (AUC0-∞=6.8 μg.h.mL-1), accepted elimination half-life (T1/2=3.5 h), and well clearance (1.18 L.h-1.kg-1), has a moderate oral bioavailability (74%) in mouse[1].
c-Met-IN-14 (i.p.; below 200 mg/kg) doesn’t cause abnormalities, anaphylactic responses, allergic reactions on mice[1].
| Animal Model: | 8-week-old male BALB/c mice [1] | | Dosage: | 0 (vehicle), 100, 200, 300, or 400 mg/kg | | Administration: | Intraperitoneal injection; treatment on day 0 and assessment every 3 days for 15 days | | Result: | Showed no obvious toxicity in acute toxicity tests. |
| Animal Model: | Pharmacokinetic profiles of compound 26af in BALB/c mouse[1]
| | Dosage: | | | Administration: | | | Result: | | Route | Dose (mg/kg) | T1/2 (h) | Cmax (ng.mL-1) | Tmax (h) | AUC0-∞ (μg.h.mL-1) | CL (L.h-1.kg-1) | CL (%) | | i.v. | 2 | 1.8 | 675.6 | - | 2.3 | - | | | p.o. | 8 | 3.5 | 1228.4 | 2.5 | 6.8 | 1.18 | 74 |
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| [References]
[1] Nan X, et al. Design, synthesis and biological evaluation of novel N-sulfonylamidine-based derivatives as c-Met inhibitors via Cu-catalyzed three-component reaction. Eur J Med Chem. 2020 Aug 15. 200:112470. DOI:10.1016/j.ejmech.2020.112470 |
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