| Identification | Back Directory | [Name]
Benzonitrile, 3-[1,6-dihydro-1-[[3-[5-[(1-methyl-4-piperidinyl)methoxy]-2-pyrimidinyl]phenyl]methyl]-6-oxo-3-pyridazinyl]-, hydrochloride (1:) | [CAS]
1103508-80-0 | [Synonyms]
Tepotinib hydrochloride(1 : x)
Benzonitrile, 3-[1,6-dihydro-1-[[3-[5-[(1-methyl-4-piperidinyl)methoxy]-2-pyrimidinyl]phenyl]methyl]-6-oxo-3-pyridazinyl]-, hydrochloride (1:) | [Molecular Formula]
C29H29ClN6O2 | [MOL File]
1103508-80-0.mol | [Molecular Weight]
529.04 |
| Hazard Information | Back Directory | [Uses]
Tepotinib (EMD-1214063) hydrochloride is an orally active and highly selective, reversible, ATP-competitive c-Met inhibitor with an IC50 of 3 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. Tepotinib hydrochloride inhibits c-Met phosphorylation and induces autophagy. Tepotinib hydrochloride has antitumor effects[1][2][3]. | [in vivo]
Tepotinib hydrochloride induces tumor regression in xenograft models and inhibits in vivo c-Met phosphorylation[1].
| Animal Model: | CD-1 or BALB/C nude mice bearing human cancer cell lines KP-4, or EBC-1[1] | | Dosage: | 6 and 15 mg/kg for mice bearing NSCLC EBC-1; 25, 50 and 200 mg/kg for mice bearing pancreatic carcinoma cell line KP-4. | | Administration: | Injected daily; for 14-18 days | | Result: | Daily administration of 5 or 15 mg/kg to EBC-1 tumor-bearing mice resulted in effective inhibition or complete tumor regression, respectively.
Induced dose-dependent tumor growth inhibition in mice bearing human pancreatic carcinoma KP-4 tumors. |
| [References]
[1] Bladt F, et al. EMD 1214063 and EMD 1204831 constitute a new class of potent and highly selective c-Met inhibitors. Clin Cancer Res, 2013, 19(11), 2941-2951. DOI:10.1158/1078-0432.CCR-12-3247
[2] Zhan N, et al. The Effect of Selective c-MET Inhibitor on Hepatocellular Carcinoma in the MET-Active, β-Catenin-Mutated Mouse Model. Gene Expr. 2018 May 18;18(2):135-147. DOI:10.3727/105221618X15174108894682
[3] A. Naing, et al. IS4-1 - A Phase I Dose-Escalation Study of emd 1214063, an Oral Selective CMET Inhibitor, in Patients with Advanced Solid Tumors. Annals of Oncology. Volume 23, Supplement 11, October 2012, Page xi21. |
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