| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
MET kinase-IN-2 targets the MET (c-MET) receptor tyrosine kinase, a key oncogenic driver in various human cancers. With an IC50 of 7.4 nM, it potently inhibits MET kinase activity and also shows activity against AXL, Flt4, KDR, Mer, TEK, and TYRO3 with IC50s ranging from 16.5 to 198 nM.
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| ln Vitro |
With IC50s ranging from 2.9 to 4.5 μM, MET kinase-IN-2 (compound 20j; 72 hours) inhibits the following cell lines: MKN-45, HT-29, NIH-H460, and U-87 MG[1]. IC50s for MET kinase-IN-2 range from 16.5 to 198 nM, and it inhibits AXL, Flt4, KDR, Mer, TEK, and TYRO3[1].
In vitro, MET kinase-IN-2 (compound 20j; 72 hours) inhibits the proliferation of U-87 MG (glioblastoma), NCI-H460 (lung), HT-29 (colorectal), and MKN-45 (gastric) cancer cell lines with IC50s ranging from 2.9 to 4.5 microM. It inhibits AXL, Flt4, KDR, Mer, TEK, and TYRO3 with IC50s ranging from 16.5 to 198 nM. |
| ln Vivo |
In the U-87 MG 24 xeograft model, MET kinase-IN-2 (3-37.5 mg/kg; po; 7 days per week for 3 weeks) shows statistically significant tumor growth inhibition[1]. The Cmax, AUC0-∞, T1/2, CL, and F% values after MET kinase-IN-2 therapy are 1.5 µg/mL, 10.7 µg·h/mL, 4.9 hours, 0.5 L/h/kg, and F=32%, respectively[1].
In vivo, MET kinase-IN-2 (3-37.5 mg/kg; oral administration; 7 days per week for 3 weeks) exhibits statistically significant tumor growth inhibition in the U-87 MG (glioblastoma) xenograft model. The antitumor activity is dose-dependent, with the highest dose showing maximal TGI. |
| Enzyme Assay |
A biochemical MET kinase inhibition assay is performed using purified recombinant MET kinase domain. Increasing concentrations of MET kinase-IN-2 (0.1 nM to 10 uM) are pre-incubated with the enzyme and ATP. A peptide substrate is added, and after a set reaction time (e.g., 60 minutes), the amount of phosphorylated product is measured using an ADP-Glo or HTRF detection system to calculate the 7.4 nM IC50. For other kinases, a similar protocol is used.
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| Cell Assay |
For cell proliferation assays, U-87 MG, NCI-H460, HT-29, and MKN-45 cells are seeded in 96-well plates and allowed to attach overnight. Cells are treated with a dilution series of MET kinase-IN-2 (0.1 uM to 50 uM) for 72 hours. Cell viability is measured using the MTT or CellTiter-Glo assay, and IC50 values (2.9-4.5 microM) are calculated from dose-response curves. For pathway analysis, cells are treated for 2-6 hours and analyzed by Western blot for p-MET, p-AKT, and p-ERK.
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| Animal Protocol |
Animal/Disease Models: 4-6 weeks old Female nude mice (U-87 MG xenograft model)[1]
Doses: 3, 6, 12.5, 37.5 mg/kg Route of Administration: Po; 7 days per week for 3 weeks Experimental Results: Induced dose-dependent tumor growth inhibition. Animal/Disease Models: Male SD rats[1] Doses: 5 mg/kg Route of Administration: Po (pharmacokinetic/PK Analysis) Experimental Results: Displayed favorable overall PK profiles, with maximal plasma concentration (Cmax=1.5 µg/mL, 5-fold higher to that of IV), plasma exposure (AUC0-∞=10.7 µg·h/mL, 9.7-fold higher to that of IV), half-life (T1/2=4.9 h, 4.9-fold longer to that of IV), total clearance CL (0.5 L/h/kg; 10-fold lower to that of IV), and oral bioavailability (F=32%, 2.7-fold higher to that of IV) after oral dose of 5 mg /kg (10 mg/kg for IV). In the U-87 MG xenograft model, female BALB/c nude mice bearing subcutaneous U-87 MG tumors (∼200 mm3) are randomized. MET kinase-IN-2 is administered orally via gavage at doses of 3, 12.5, 25, and 37.5 mg/kg once daily, 7 days per week for 3 weeks. Tumor volumes are measured bi-weekly with calipers. At study endpoint, tumors are excised, weighed, and TGI is calculated. MET kinase-IN-2 treatment shows Cmax of 1.5 ug/mL, AUC0-∞ of 10.7 ug·h/mL, T1/2 of 4.9 hours, CL of 0.5 L/h/kg, and oral bioavailability (F%) of 32%. These values indicate moderate oral absorption and a half-life suitable for once-daily dosing. |
| Toxicity/Toxicokinetics |
No specific toxicology data beyond monitoring body weight during efficacy studies is reported for MET kinase-IN-2. Body weight measurements in animal studies indicate tolerability at the tested doses (3-37.5 mg/kg).
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| References | |
| Additional Infomation |
MET kinase-IN-2 (CAS: 2101241-90-9) is a potent, selective, orally bioavailable MET kinase inhibitor with an IC50 of 7.4 nM and antitumor activity. It inhibits proliferation of U-87 MG, NCI-H460, HT-29, and MKN-45 cells (IC50s: 2.9-4.5 microM) and shows significant tumor growth inhibition in the U-87 MG xenograft model. PK parameters: Cmax 1.5 ug/mL, AUC0-∞ 10.7 ug·h/mL, T1/2 4.9 h, CL 0.5 L/h/kg, F% = 32%. Molecular formula: C33H27FN4O4; molecular weight: 562.59.
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| Molecular Formula |
C33H27FN4O4
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| Molecular Weight |
562.590291261673
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| Exact Mass |
562.201
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| CAS # |
2101241-90-9
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| PubChem CID |
134401435
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
42
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| Complexity |
958
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1C2=C(C(NC3=CC=C(OC4C5C(N=CC=4)=CC(OCC(O)(C)C)=CC=5)C(F)=C3)=NC=C2)C(=O)C(C2=CC=CC=C2)=C1
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| InChi Key |
DGRCFAYRKDYEMX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C33H27FN4O4/c1-33(2,40)19-41-22-9-10-23-27(17-22)35-15-13-28(23)42-29-11-8-21(16-25(29)34)38-32-30-26(12-14-36-32)37-18-24(31(30)39)20-6-4-3-5-7-20/h3-18,40H,19H2,1-2H3,(H,36,38)(H,37,39)
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| Chemical Name |
5-[3-fluoro-4-[7-(2-hydroxy-2-methylpropoxy)quinolin-4-yl]oxyanilino]-3-phenyl-1H-1,6-naphthyridin-4-one
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMSO: 100 mg/mL (177.75 mM)
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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 | 1.7775 mL | 8.8875 mL | 17.7749 mL | |
| 5 mM | 0.3555 mL | 1.7775 mL | 3.5550 mL | |
| 10 mM | 0.1777 mL | 0.8887 mL | 1.7775 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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