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| 100mg |
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Purity: ≥98%
| ln Vitro |
At a dose of around 4 nM and an IC50 value of about 1 nM, capmatinib (INCB28060) inhibits c-MET phosphorylation. Over 90% of c-MET is inhibited by it. This is reversible, and hours after the substance is removed, the effect is greatly diminished. 48 hours later, entirely vanishes [1]. Capmatinib (INCB28060) (0–1000 nM; 72 hours) inhibits SNU-5, S114, H441, and U-87MG from proliferating [1]. The phosphorylation of c-MET and downstream effectors of the c-MET pathway, including ERK1/2, AKT, FAK, GAB1, and STAT3/5, is efficiently inhibited by capmatinib (INCB28060) (0.06-62.25 nM; 2h) [1]. The inhibitor capmatinib (INCB28060) (0.24-63 nM; over night) stops HGF-induced migration of H441 cells [1]. Capmatinib (INCB28060) suppresses EGFR and HER-3 phosphorylation quickly (0.5–50 nM; 20 minutes) [1]. In SNU-5 cells, capmatinib (INCB28060) (0-333 nM; 24 hours) causes apoptosis [1].
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| ln Vivo |
Capmatinib (INCB28060) (1-30 mg/kg; orally, twice daily for 2 weeks) displayed dose-dependent reduction of tumor development and was well tolerated at all dosages during treatment , there was no evidence of overt toxicity or body weight loss in the U-87MG tumor mouse model [1]. Capmatinib (INCB28060) (0.03-10 mg/kg; oral, single dosage) suppresses c-MET phosphorylation in the S114 tumor mouse model [1].
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: SNU-5, S114, H441 and U-87MG Tested Concentrations: 0-10000 nM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition of cell viability and colony formation of SNU-5 and S114 H441 and U-87MG The IC50 values are 1.2 nM, 12.4 nM, ~0.5 nM and 2 nM respectively. Cell migration assay[1] Cell Types: H441 (stimulated with 50 ng/mL recombinant human HGF for 24 hrs (hours)) Tested Concentrations: 0.24, 1, 4, 16 and 63 nM Incubation Duration: Overnight Experimental Results: Prevents HGF-stimulated H441 cell migration, IC50 Approximately 2 nM, and cell migration is 16 nM. Western Blot Analysis[1] Cell Types: SNU-5 Tested Concentrations: 0.06, 0.24, 0.98, 3.91, 15.63 and 62.25 nM Incubation Duration: 2 hrs (hours) Experimental Results: Effectively inhibits c-MET and the phosphorylation of downstream effectors of the c-MET pathway such as ERK1/2, AKT, FAK, GAB1 and STAT3/5. Western Blot Analysis[1] Cell Types: H1993 Cell Tested Concentrations: 0.5, 5 and 50 nM Incubation Duration: 20 minutes Experimental Results: Rapidly inhibits the phosphorylation of EGFR and HER- |
| Animal Protocol |
Animal/Disease Models: Female Balb/c nu/nu (nude) mice (subcutaneously (sc) (sc) inoculated with 5×106 U-87MG glioblastoma cells) [1]
Doses: 1, 3, 10 and 30 mg/kg Route of Administration: Orally, daily Two times for 2 weeks. Experimental Results: 1 mg/kg and 3 mg/kg one time/day had a dose-dependent inhibitory effect on tumor growth, which was 35% and 76% respectively; among 10 U-87MG tumor-bearing mice, Six animals experienced partial regression after taking the 10 mg/kg daily dose; and all doses were well tolerated during treatment, with no evidence of significant toxicity or weight loss. Animal/Disease Models: Female Balb/c nu/nu (nude) mice (subcutaneously (sc) (sc) inoculated with 4×106 S114 tumor cells) [1] Doses: 0.03, 0.1, 0.3, 1, 3 and 10 mg/kg Doses: po (po (oral gavage)) single dose Experimental Results: Causes approximately 50% and 90% inhibition of c-MET phosphorylation 30 minutes after administration of 0.03 and 0.3 mg/kg, and more than 90% inhibition of phosphorylation of c-MET after 7 hrs (hrs (hours)). |
| References |
[1]. Liu X, et al. A novel kinase inhibitor, INCB28060, blocks c-MET-dependent signaling, neoplastic activities, and cross-talk with EGFR and HER-3. Clin Cancer Res. 2011 Nov 15;17(22):7127-38.
[2]. Baltschukat S, et al. Capmatinib (INC280) Is Active Against Models of Non-Small Cell Lung Cancer and Other Cancer Types with Defined Mechanisms of MET Activation. Clin Cancer Res. 2019 May 15;25(10):3164-3175. [3]. Dhillon S. Capmatinib: First Approval. Drugs. 2020 Jul;80(11):1125-1131. |
| Molecular Formula |
C23H18CLFN6O
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|---|---|
| Molecular Weight |
448.880026340485
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| CAS # |
1029714-89-3
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| Related CAS # |
Capmatinib;1029712-80-8;Capmatinib dihydrochloride hydrate;1865733-40-9;Capmatinib dihydrochloride;1197376-85-4
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| SMILES |
Cl.FC1=C(C(NC)=O)C=CC(=C1)C1C=NC2=NC=C(CC3C=CC4C(=CC=CN=4)C=3)N2N=1
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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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2278 mL | 11.1388 mL | 22.2777 mL | |
| 5 mM | 0.4456 mL | 2.2278 mL | 4.4555 mL | |
| 10 mM | 0.2228 mL | 1.1139 mL | 2.2278 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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