| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| 100mg |
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| 500mg |
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| 1g |
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| Targets |
The primary target of tepotinib is c-Met (hepatocyte growth factor receptor), a receptor tyrosine kinase that plays a critical role in cell proliferation, survival, migration, and invasion. Tepotinib is an ATP-competitive, reversible inhibitor that binds to the kinase domain of c-Met, preventing its phosphorylation and downstream signaling. It is highly selective for c-Met, showing >200-fold selectivity over other kinases including IRAK4, TrkA, Axl, IRAK1, and Mer.
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| ln Vitro |
In vitro, tepotinib inhibits c-Met with an IC₅₀ of 3 nM. It is >200-fold more selective for c-Met than for IRAK4, TrkA, Axl, IRAK1, and Mer. Tepotinib inhibits c-Met phosphorylation and induces autophagy in cancer cells. Its high potency and selectivity make it a promising therapeutic agent for c-Met-driven cancers, including non-small cell lung cancer with MET exon 14 skipping mutations.
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| ln Vivo |
In vivo, tepotinib is an orally active c-Met inhibitor. It has demonstrated antitumor activity in preclinical models of c-Met-driven cancers. Tepotinib has received regulatory approval in several countries for the treatment of adult patients with metastatic non-small cell lung cancer harboring MET exon 14 skipping alterations. Its oral bioavailability and favorable pharmacokinetic profile support once-daily dosing in clinical practice.
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| Enzyme Assay |
In vitro non-cellular enzyme assays for tepotinib typically involve kinase inhibition studies. A common protocol is: (1) prepare recombinant c-Met kinase domain; (2) incubate the kinase with ATP, substrate peptide, and tepotinib at various concentrations (0.1-1000 nM); (3) measure kinase activity using radioactive (³²P-ATP) or luminescent (ADP-Glo) detection; (4) calculate IC₅₀ values from dose-response curves; (5) assess selectivity against a panel of kinases (including IRAK4, TrkA, Axl, IRAK1, Mer, and others); and (6) determine the mechanism of inhibition (ATP-competitive) by kinetic analysis.
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| Cell Assay |
In vitro cell-based assays for tepotinib typically involve: (1) culture c-Met-dependent cancer cell lines (e.g., EBC-1, Hs746T, or others with MET amplification or exon 14 skipping) in appropriate medium; (2) treat cells with tepotinib at various concentrations (0.1-1000 nM) for 2-72 hours; (3) assess cell viability using MTT or CellTiter-Glo assays; (4) measure c-Met phosphorylation by Western blot or ELISA; (5) evaluate downstream signaling (AKT, MAPK pathways); (6) assess apoptosis and autophagy induction; and (7) calculate IC₅₀ values for cell growth inhibition.
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| Animal Protocol |
In vivo animal experiments with tepotinib typically involve xenograft models. A common protocol is: (1) inject c-Met-driven cancer cells subcutaneously into immunocompromised mice; (2) allow tumors to establish to a volume of ~150-200 mm³; (3) administer tepotinib orally at doses of 10-100 mg/kg once daily; (4) monitor tumor growth by caliper measurements; (5) assess c-Met phosphorylation in tumors by immunohistochemistry; (6) evaluate tumor apoptosis and proliferation (Ki67, TUNEL); (7) determine maximum tolerated dose and efficacy compared to vehicle controls; and (8) assess pharmacokinetic parameters in plasma and tumor tissue.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of tepotinib: It is an orally active compound with good oral bioavailability. The hydrochloride hydrate form has a molecular weight of 547.1. In patients, tepotinib is administered orally once daily. It is metabolized primarily by CYP3A4 and has a half-life of approximately 20-30 hours. It is highly protein-bound (>99%). Food intake does not significantly affect its absorption. Tepotinib is eliminated primarily via the liver.
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| Toxicity/Toxicokinetics |
The toxicity profile of tepotinib is well-characterized from clinical trials. Common adverse effects include peripheral edema, nausea, diarrhea, fatigue, and elevated liver enzymes. Serious adverse effects include interstitial lung disease, hepatotoxicity, and pancreatitis. Tepotinib is contraindicated in patients with hypersensitivity to the active substance. It is approved for the treatment of MET exon 14 skipping non-small cell lung cancer.
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| Additional Infomation |
This compound is also known as tepotinib hydrochloride monohydrate and EMD-1214063. It is an orally active, highly selective, reversible, ATP-competitive c-Met inhibitor. The molecular formula is C₂₉H₂₈N₆O₂·HCl·H₂O and the molecular weight is 547.1. Tepotinib is approved for the treatment of MET exon 14 skipping non-small cell lung cancer. The UNII is VY5YX2TQ1F.
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| Molecular Formula |
C29H31CLN6O3
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|---|---|
| Molecular Weight |
547.047845125198
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| Exact Mass |
546.215
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| CAS # |
1946826-82-9
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| Related CAS # |
Tepotinib hydrochloride; 1103508-80-0; Tepotinib; 1100598-32-0
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| PubChem CID |
46700774
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
2
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
39
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| Complexity |
880
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CCC(CC1)COC2=CN=C(N=C2)C3=CC=CC(=C3)CN4C(=O)C=CC(=N4)C5=CC=CC(=C5)C#N.O.Cl
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| InChi Key |
KZVOMLRKFJUTLK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H28N6O2.ClH.H2O/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;1H;1H2
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| Chemical Name |
3-[1-[[3-[5-[(1-methylpiperidin-4-yl)methoxy]pyrimidin-2-yl]phenyl]methyl]-6-oxopyridazin-3-yl]benzonitrile;hydrate;hydrochloride
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8280 mL | 9.1399 mL | 18.2799 mL | |
| 5 mM | 0.3656 mL | 1.8280 mL | 3.6560 mL | |
| 10 mM | 0.1828 mL | 0.9140 mL | 1.8280 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.
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.
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