| CAS NO: | 1100598-32-0 |
| 规格: | ≥98% |
| Molecular Weight (MW) | 492.57 |
|---|---|
| Formula | C29H28N6O2 |
| CAS No. | 1100598-32-0 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: 5 mg/mL (10.2 mM) |
| Water: <1 mg/mL | |
| Ethanol: <1 mg/mL | |
| Solubility (In vivo) | 5% DMSO+corn oil: 5mg/mL |
| Synonyms | EMD-1214063, MSC-2156119; EMD1214063; EMD 1214063; MSC2156119; MSC 2156119; Tepotinib. IUPAC/Chemical Name: 3-(1-(3-(5-((1-methylpiperidin-4-yl)methoxy)pyrimidin-2-yl)benzyl)-1,6-dihydro-6-oxopyridazin-3-yl)benzonitrile InChi Key: AHYMHWXQRWRBKT-UHFFFAOYSA-N InChi Code: InChI=1S/C29H28N6O2/c1-34-12-10-21(11-13-34)20-37-26-17-31-29(32-18-26)25-7-3-5-23(15-25)19-35-28(36)9-8-27(33-35)24-6-2-4-22(14-24)16-30/h2-9,14-15,17-18,21H,10-13,19-20H2,1H3 SMILES Code: N#CC1=CC=CC(C(C=C2)=NN(CC3=CC=CC(C4=NC=C(OCC5CCN(C)CC5)C=N4)=C3)C2=O)=C1 |
| In Vitro | In vitro activity: EMD 1214063 inhibits HGF-induced c-Met phosphorylation in A549 cells with IC50 of 6 nM. Treatment with EMD 1214063 induces a marked reduction of c-Met–constitutive phosphorylation in EBC-1 cells with IC50 of 9 nM. EMD 1214063 effectively blocka phosphorylation of the major downstream effectors of the c-Met enzyme, such as Grb2, Gab1, Sos, PLCγ, and phosphoinositide 3-kinase, in EBC-1, MKN-45, and Hs746T cells in the range of 1 to 10 nM. EMD 1214063 considerably inhibits the viability of MKN-45 cells with IC50 of less than 1 nM. Treatment with EMD 1214063 (as low as 0.1 nM) inhibits HGF-induced NCI-H441 cell migration, whereas concentrations of 100 nM to 1 μM almost completely prevents it. Kinase Assay: Tepotinib (EMD-1214063) is a potent and selective c-Met inhibitor with IC50 of 4 nM,>200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. |
|---|---|
| In Vivo | EMD 1214063 treatment, at doses of 10 mg/kg or more, results in more than 90% inhibition of c-Met phosphorylation in Hs746T xenograft tumor for a period of at least 72 hours. EMD 1214063 induces more than 50% reduction of cyclin D1 expression, which persists after 96 hours upon treatment with doses of 100 mg/kg. A transient induction of p27 and cleaved caspase-3 are also observed upon treatment with EMD 1214063. EMD 1214063 (15 mg/kg, daily) treatment induces complete regression of gastric carcinoma xenografts Hs746T, in which c-Met is amplified, overexpressed, and activated in a ligand-independent fashion. |
| Animal model | Xenografts Hs746T |
| Formulation & Dosage | 15 mg/kg |
| References | Clin Cancer Res. 2013 Jun 1;19(11):2941-51 |
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