EMD-1214063

• CAT Number: I000414
• CAS Number: 1100598-32-0
• Molecular Formula: C₂₉H₂₈N₆O₂
• Molecular Weight: 492.57
• Purity: ≥95%
• Target: c-MET
• Solubility: DMSO: ≤ 27 mg/mL
• Storage: 3 years -20℃ powder
• IC50: 4 nM [1]
• IUPAC Name: 3-[1-[[3-[5-[(1-methylpiperidin-4-yl)methoxy]pyrimidin-2-yl]phenyl]methyl]-6-oxopyridazin-3-yl]benzonitrile
• InChI: 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
• InChIKey: AHYMHWXQRWRBKT-UHFFFAOYSA-N
• SMILES: CN1CCC(CC1)COC2=CN=C(N=C2)C3=CC(=CC=C3)CN4C(=O)C=CC(=N4)C5=CC=CC(=C5)C#N

Tepotinib (Cat.No:I000414), also known as EMD 1214063 and MSC2156119, is an inhibitor of MET tyrosine kinase with potential antineoplastic activity. MET tyrosine kinase inhibitor EMD 1214063 selectively binds to MET tyrosine kinase and disrupts MET signal transduction pathways, which may induce apoptosis in tumor cells overexpressing this kinase.

Reference

1:Clin Cancer Res. 2013 Jun 1;19(11):2941-51. doi: 10.1158/1078-0432.CCR-12-3247. Epub 2013 Apr 3. EMD 1214063 and EMD 1204831 constitute a new class of potent and highly selective c-Met inhibitors.Bladt F,Faden B,Friese-Hamim M,Knuehl C,Wilm C,Fittschen C,Grädler U,Meyring M,Dorsch D,Jaehrling F,Pehl U,Stieber F,Schadt O,Blaukat A, PMID: 23553846 DOI: 10.1158/1078-0432.CCR-12-3247
Abstract: PURPOSE: The mesenchymal-epithelial transition factor (c-Met) receptor, also known as hepatocyte growth factor receptor (HGFR), controls morphogenesis, a process that is physiologically required for embryonic development and tissue repair. Aberrant c-Met activation is associated with a variety of human malignancies including cancers of the lung, kidney, stomach, liver, and brain. In this study, we investigated the properties of two novel compounds developed to selectively inhibit the c-Met receptor in antitumor therapeutic interventions.EXPERIMENTAL DESIGN: The pharmacologic properties, c-Met inhibitory activity, and antitumor effects of EMD 1214063 and EMD 1204831 were investigated in vitro and in vivo, using human cancer cell lines and mouse xenograft models.RESULTS: EMD 1214063 and EMD 1204831 selectively suppressed the c-Met receptor tyrosine kinase activity. Their inhibitory activity was potent [inhibitory 50% concentration (IC50), 3 nmol/L and 9 nmol/L, respectively] and highly selective, when compared with their effect on a panel of 242 human kinases. Both EMD 1214063 and EMD 1204831 inhibited c-Met phosphorylation and downstream signaling in a dose-dependent fashion, but differed in the duration of their inhibitory activity. In murine xenograft models, both compounds induced regression of human tumors, regardless of whether c-Met activation was HGF dependent or independent. Both drugs were well tolerated and induced no substantial weight loss after more than 3 weeks of treatment.CONCLUSIONS: Our results indicate selective c-Met inhibition by EMD 1214063 and EMD 1204831 and strongly support clinical testing of these compounds in the context of molecularly targeted anticancer strategies.