Tepotinib (EMD 1214063; MSC 2156119)

Alias: EMD-1214063; MSC-2156119; EMD1214063; EMD 1214063; MSC2156119; MSC 2156119; Tepotinib
Cat No.:V0596 Purity: ≥98%
This product has been discontinued. Tepotinib (formerly EMD 1214063, EMD-1214063; MSC2156119; MSC-2156119; Tepmetko) is a selective c-Met inhibitor with potential antineoplastic activity.
Tepotinib (EMD 1214063; MSC 2156119) Chemical Structure CAS No.: 1100598-32-0
Product category: c-MET
This product is for research use only, not for human use. We do not sell to patients.
Size Price
Discontinued
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

This product has been discontinued. Tepotinib (formerly EMD 1214063, EMD-1214063; MSC2156119; MSC-2156119; Tepmetko) is a selective c-Met inhibitor with potential antineoplastic activity. Tepotinib has been approved for the treatment of adults with metastatic non-small cell lung cancer whose tumors have a mutation that causes exon 14 skipping in the mesenchymal-epithelial transition in 2020 in Japan and in the USA in 2021. With an IC50 of 4 nM, it exhibits >200-fold selectivity in inhibiting c-Met relative to other kinases, including IRAK4, TrkA, Axl, IRAK1, and Mer. In A549 cells, tecitinib has an average IC50 of 6 nM to suppress HGF-induced c-Met phosphorylation. Moreover, it strongly suppresses the phosphorylation of Akt, Gab-1, and Erk1/2, as well as the activation of downstream signaling pathways of c-Met.

Biological Activity I Assay Protocols (From Reference)
Targets
c-Met (IC50 = 4 nM)
ln Vitro

EMD 1214063 has an IC50 of 6 nM and inhibits HGF-induced c-Met phosphorylation in A549 cells. EMD 1214063 treatment significantly reduces c-Met constitutive phosphorylation in EBC-1 cells, with an IC50 of 9 nM. In the range of 1 to 10 nM, EMD 1214063 efficiently blocks the phosphorylation of the main downstream effectors of the c-Met enzyme in EBC-1, MKN-45, and Hs746T cells, including Grb2, Gab1, Sos, PLCγ, and phosphoinositide 3-kinase. With an IC50 of less than 1 nM, EMD 1214063 significantly reduces MKN-45 cell viability. HGF-induced NCI-H441 cell migration is inhibited by EMD 1214063 treatment at as low as 0.1 nM, while it is nearly entirely prevented at concentrations of 100 nM to 1 μM. [1]

ln Vivo
EMD 1214063 treatment causes c-Met phosphorylation in Hs746T xenograft tumors to be more than 90% inhibited for at least 72 hours at doses of 10 mg/kg or higher. When treated with doses of 100 mg/kg, EMD 1214063 causes a more than 50% reduction in cyclin D1 expression, which lasts for 96 hours. Following treatment with EMD 1214063, a brief induction of p27 and cleaved caspase-3 are also seen. Treatment with EMD 1214063 (15 mg/kg, daily) results in total regression of gastric carcinoma xenografts Hs746T, wherein c-Met is overexpressed, amplified, and activated in a manner that is independent of ligands. [1]
Cell Assay
Tepotinib (EMD-1214063) is a c-Met inhibitor that is both potent and selective. With an IC50 of 4 nM, it is >200 times more selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer.
Animal Protocol
Human gastric carcinoma xenografts Hs746T
15 mg/kg
daily
References

[1]. Clin Cancer Res . 2013 Jun 1;19(11):2941-51.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C29H28N6O2
Molecular Weight
492.57
Exact Mass
492.22737416
CAS #
1100598-32-0
SMILES
CN1CCC(CC1)COC2=CN=C(N=C2)C3=CC=CC(=C3)CN4C(=O)C=CC(=N4)C5=CC=CC(=C5)C#N
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
Chemical Name
3-[1-[[3-[5-[(1-methylpiperidin-4-yl)methoxy]pyrimidin-2-yl]phenyl]methyl]-6-oxopyridazin-3-yl]benzonitrile
Synonyms
EMD-1214063; MSC-2156119; EMD1214063; EMD 1214063; MSC2156119; MSC 2156119; Tepotinib
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
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
 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.0302 mL 10.1508 mL 20.3017 mL
5 mM 0.4060 mL 2.0302 mL 4.0603 mL
10 mM 0.2030 mL 1.0151 mL 2.0302 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03940703 Active
Recruiting
Drug: Tepotinib
Drug: Osimertinib
Non-small Cell Lung Cancer EMD Serono Research & Development
Institute, Inc.
September 19, 2019 Phase 2
NCT02864992 Active
Recruiting
Drug: Tepotinib Lung Adenocarcinoma Stage IIIB/IV
Amplification
EMD Serono Research & Development
Institute, Inc.
September 13, 2016 Phase 2
NCT05120960 Recruiting Drug: tepotinib plus osimertinib
Drug: tepotinib
Brain Tumor M.D. Anderson Cancer Center February 27, 2023 Phase 1
NCT04647838 Recruiting Drug: Tepotinib Solid Tumor
MET Amplification
Chungbuk National University
Hospital
January 16, 2020 Phase 2
NCT05782361 Recruiting Drug: Tepotinib
Drug: Pembrolizumab
Non Small Cell Lung Cancer
Advanced Cancer
Institute of Cancer Research,
United Kingdom
May 3, 2023 Phase 1
Biological Data
  • Tepotinib (EMD 1214063)

    Dose-dependent inhibition of c-Met auto-phosphorylation in vivo. Clin Cancer Res. 2013 Jun 1;19(11):2941-51.

  • Tepotinib (EMD 1214063)

    EMD 1214063 and EMD 1204831 effectively inhibit tumor c-Met auto-phosphorylation and cyclin D1 expression while inducing p27 expression. Clin Cancer Res. 2013 Jun 1;19(11):2941-51.

  • Tepotinib (EMD 1214063)

    EMD 1214063 and EMD 1204831 display antitumor activity in HGF-dependent and HGF-independent xenograft tumor models. Clin Cancer Res. 2013 Jun 1;19(11):2941-51.

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