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c-Met-IN-14
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c-Met-IN-14
CAS No. : 2443380-34-3
MCE 站:c-Met-IN-14
产品活性:c-Met-IN-14 (compound 26af) 是 N- 磺酰胺基衍生物,是一种 c-Met 激酶抑制剂,IC50 为 2.89 nM。c-Met-IN-14 通过阻断 c-Met 的磷酸化表现出抗癌活性,并将细胞周期阻滞在 G2/M 期。c-Met-IN-14 呈剂量依赖性诱导 A549 细胞凋亡 (apoptosis)。
研究领域:Protein Tyrosine Kinase/RTK | Apoptosis
作用靶点:c-Met/HGFR | c-Kit | FLT3 | Apoptosis
In Vitro: c-Met-IN-14 (compound 26af) is a relatively selective inhibitor of c-Met kinase (IC50=2.89 nM), because of high inhibitory effects against c-Kit (IC50=4.26 nM) and Flt-3 (IC50=7.28 nM).
c-Met-IN-14 (0.28-0.72 μM; 24 h) exhibits the remarkable anti-proliferative activities against cancer cell lines (A549, HT-29, MKN-45 and MDA-MB-231), with IC50s of 0.28-0.72 μM.
c-Met-IN-14 (0.25, 0.5, and 1.0 μM; 12 h) induces the late apoptotic and early apoptotic and (0.25, 0.5, and 1.0 μM; 24 h) shows anti-proliferative of A549 cells by arresting cell cycle at G2/M phase and apoptosis induction.
c-Met-IN-14 (1.35, or 6.12 μM, respectively; 24 h) has moderate selectivity towards cancer cells over normal cells, with the selectivity index of 4.2 and 19.1 to HUVEC (IC50=1.35 μM) and FHC cells (IC50=6.12 μM), respectively.
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 g.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.
c-Met-IN-14 (i.p.; below 200 mg/kg) doesn’t cause abnormalities, anaphylactic responses, allergic reactions on mice.
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