SGX-523 |
| رقم الكتالوجGC15664 |
SGX523 هو مثبط MET انتقائي بشكل رائع وتنافسي ATPيثبط SGX523 بشكل فعال MET مع IC50 لـ 4 نانومتر وهو> 1000 ضعف انتقائي مقابل كينازات البروتين الأخرىنشاط انتيتومور
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1022150-57-7
Sample solution is provided at 25 µL, 10mM.
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SGX-523 is a novel, potent, ATP-competitive, and highly-selective Hepatocyte growth factor receptor (MET) inhibitor with IC50 value of 4 nM [1].
SGX523 inhibits MET autophosphorylation in gastric cancer cell line GTL16 and human lung carcinoma cell line A549, with IC50 of 40 nM and 12 nM, respectively [1]. Additionally, tumor regression was observed in gastic cancer cell line GTL16 and human GBM cell line U87MG derived mouse xenograft models that are treated with SGX-523 by oral gavage [1].
SGX523 has been shown to inhibit the phosphorylateion of MEK, MAPK, AKT in brain cancer cell lines including U87, U373, DAOY, as well as glioma stem cells 1228. The inhibition of MEK in brain cancer cells and stem cells led to cell proliferation, G1/S cell cycle progression, cell migration, and cell invasion [2].
References:
[1] Buchanan SG1, Hendle J, Lee PS, Smith CR, Bounaud PY, Jessen KA, Tang CM, Huser NH, Felce JD, Froning KJ, Peterman MC, Aubol BE, Gessert SF,Sauder JM, Schwinn KD, Russell M, Rooney IA, Adams J, Leon BC, Do TH, Blaney JM, Sprengeler PA, Thompson DA, Smyth L, Pelletier LA, Atwell S, Holme K,Wasserman SR, Emtage S, Burley SK, Reich SH. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol Cancer Ther. 2009 Dec;8(12):3181-90.
[2] Guessous F1, Zhang Y, diPierro C, Marcinkiewicz L, Sarkaria J, Schiff D, Buchanan S, Abounader R.An orally bioavailable c-Met kinase inhibitor potently inhibits brain tumor malignancy and growth. Anticancer Agents Med Chem. 2010 Jan;10(1):28-35.
| Kinase experiment [1]: | |
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Kinase assay |
Initial rate constants were measured at 21 °C in the presence of 100 mM HEPES (pH 7.5), 0.3 mg/mL poly(Glu-Tyr) peptide substrate, 10 mM MgCl2, 1 mg/mL bovine serum albumin, 5% DMSO, 20 nM MET-KD and various concentrations of ATP and SGX523. Total reaction volumes (20 μL) were quenched with 20 μL Kinase-Glo detection buffer. Luminescence was detected in a plate-reading luminometer and the results were analyzed by nonlinear regression. |
| Cell experiment [1]: | |
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Cell lines |
MDCK cells |
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Preparation method |
The solubility of this compound in DMSO is > 18 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
0.04, 0.12, 0.36 and 3.0 μM; overnight |
|
Applications |
In MDCK canine kidney epithelial cells, SGX-523 prevented HGF-induced cell scattering. |
| Animal experiment [1]: | |
|
Animal models |
Nude mice bearing GTL16 gastric cancer cell xenografts |
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Dosage form |
10, 20, 30, 100 mg/kg, b.i.d., or 60 mg/kg, q.d.; p.o. |
|
Applications |
At the dose of ﹥ 10 mg /kg twice daily, SGX523 significantly retarded the growth of GTL16 xenografts. In addition, SGX523 substantially inhibited MET kinase activity. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Buchanan SG1, Hendle J, Lee PS, Smith CR, Bounaud PY, Jessen KA, Tang CM, Huser NH, Felce JD, Froning KJ, Peterman MC, Aubol BE, Gessert SF,Sauder JM, Schwinn KD, Russell M, Rooney IA, Adams J, Leon BC, Do TH, Blaney JM, Sprengeler PA, Thompson DA, Smyth L, Pelletier LA, Atwell S, Holme K,Wasserman SR, Emtage S, Burley SK, Reich SH. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol Cancer Ther. 2009 Dec;8(12):3181-90. | |
| Cas No. | 1022150-57-7 | SDF | |
| Chemical Name | 6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulfanyl]quinoline | ||
| Canonical SMILES | CN1C=C(C=N1)C2=NN3C(=NN=C3SC4=CC5=C(C=C4)N=CC=C5)C=C2 | ||
| Formula | C18H13N7S | M.Wt | 359.41 |
| الذوبان | ≥ 17.95mg/mL in DMSO | 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 | 2.7823 mL | 13.9117 mL | 27.8234 mL |
| 5 mM | 0.5565 mL | 2.7823 mL | 5.5647 mL |
| 10 mM | 0.2782 mL | 1.3912 mL | 2.7823 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
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
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 31 reference(s) in Google Scholar.)
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