S49076 |
| Catalog No.GC19317 |
S49076 is a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3 with IC50 values below 20 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1265965-22-7
Sample solution is provided at 25 µL, 10mM.
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S49076 is a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3 with IC50 values below 20 nM.
S49076 potently blocks cellular phosphorylation of MET, AXL, and FGFRs and inhibits downstream signaling. S49076 inhibits the proliferation of MET- and FGFR2-dependent gastric cancer cells, blocks MET-driven migration of lung carcinoma cells, and inhibits colony formation of hepatocarcinoma cells expressing FGFR1/2 and AXL. Total inhibition of MET phosphorylation is seen after 2 hours of incubation with 10 nM S49076 and an with an IC50 of 2 nM. S49076 inhibits MET phosphorylation on this site in GTL-16 gastric carcinoma cells with an IC50 value of 3 nM. The IC50 for AXL inhibition by S49076 is 56 nM. S49076 inhibits AXL signaling via AKT with an IC50 of 33 nM[1].
In tumor xenograft models, a good pharmacokinetic/pharmacodynamic relationship for MET and FGFR2 inhibition following oral administration of S49076 is established and correlated well with impact on tumor growth. MET, AXL, and the FGFRs have all been implicated in resistance to VEGF/VEGFR inhibitors such as bevacizumab. Combination of S49076 with bevacizumab in colon carcinoma xenograft models leads to near total inhibition of tumor growth. S49076 alone caused tumor growth arrest in bevacizumab-resistant tumors[1].
References:
[1]. Burbridge MF, et al. S49076 is a novel kinase inhibitor of MET, AXL, and FGFR with strong preclinical activity alone and in association with bevacizumab. Mol Cancer Ther. 2013 Sep;12(9):1749-62.
Cell experiment: | For GTL-16 and SNU-16 viability assays, cells are seeded in 96-well microplates at the appropriate density in media containing 10% FCS and supplemented 48 hours later with serial dilutions of S49076 in a final volume of 150 μL per well. After 96 hours (GTL-16) or 120 hours (SNU-16) incubation (corresponding to 4 doubling times), 15 μL of a solution of 5 mg/mL MTT is added to each well and the plates are incubated for 4 hours at 37°C. The formazan metabolite is solubilized in SDS for SNU-16 and, following removal of the MTT solution, in DMSO for GTL-16. Global cell viability is estimated by measurement of optical density at 540 nm[1]. |
Animal experiment: | Mice: Female balb/c and swiss nu/nu mice are used in the study. The hydrochloride salt of S49076 is administered orally to mice in 1% (w/v) hydroxyethylcellulose in ammonium acetate buffer pH 4.5 in a volume of 200 μL per 20 g body weight. The maximal tolerated dose of S49076 in these mice is determined to be 100 mg/kg/d (5 days a week for at least 3 weeks). Bevacizumab is dissolved in PBS and administered intraperitoneally in a volume of 200 μL per 20 g body weight[1]. |
References: [1]. Burbridge MF, et al. S49076 is a novel kinase inhibitor of MET, AXL, and FGFR with strong preclinical activity alone and in association with bevacizumab. Mol Cancer Ther. 2013 Sep;12(9):1749-62. | |
| Cas No. | 1265965-22-7 | SDF | |
| Canonical SMILES | O=C(N1CC2=CC3=C(NC(/C3=C\C4=CC(CN5CCOCC5)=CN4)=O)C=C2)SCC1=O | ||
| Formula | C22H22N4O4S | M.Wt | 438.5 |
| Solubility | DMSO : ≥ 31 mg/mL (70.70 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2805 mL | 11.4025 mL | 22.805 mL |
| 5 mM | 0.4561 mL | 2.2805 mL | 4.561 mL |
| 10 mM | 0.2281 mL | 1.1403 mL | 2.2805 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 17 reference(s) in Google Scholar.)
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