GSK1904529A (Synonyms: GSK4529) |
| رقم الكتالوجGC17612 |
GSK1904529A هو مثبط قوي ، انتقائي ، فعال عن طريق الفم ، ومانع ATP لمستقبلات عامل النمو الشبيه بالأنسولين -1 (IGF-1R) ومستقبل الأنسولين (IR) ، مع IC50s من 27 و 25 نانومتر ، على التوالي
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1089283-49-7
Sample solution is provided at 25 µL, 10mM.
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GSK1904529A is a small-molecule inhibitor of the insulin-like growth factor-I receptor (IGF-IR) with IC50 value of 27 nM 1.
GSK1904529A is a reversible and ATP-competitive inhibitor with Ki value of 1.6 nM. In NIH-3T3/LISN cells, GSK1904529A potently inhibited phosphorylation of IGF-IR with IC50 value of 22 nM. It also demonstrated to be a selective inhibitor since it showed poor inhibitory activity against 45 other serine/threonine and tyrosine kinases. When treated with whole-cell extracts, GSK1904529A significantly inhibited the ligand-induced phosphorylation of IGF-IR and decreased phosphorylation of downstream signaling including AKT, IRS-1 and ERK at concentrations > 0.01μM. GSK1904529A suppressed cell proliferation in a variety of tumor cells. The IC50 values for NCI-H929, TC-71, SK-N-MC, COLO 205, MCF7 and PREC are 81, 35, 43, 124, 137 and 68 nM, respectively. In COLO 205, MCF-7, and NCI-H929 cells, GSK1904529A treatment resulted in cell accumulation in G1 and decrease in S and G2-M phases. Moreover, in NIH-3T3/LISN xenograft model, once daily administration of GSK1904529A at 30 mg/kg inhibited 56% of tumor growth 1.
References:
1. Sabbatini P, Rowand J L, Groy A, et al. Antitumor activity of GSK1904529A, a small-molecule inhibitor of the insulin-like growth factor-I receptor tyrosine kinase. Clinical Cancer Research, 2009, 15(9): 3058-3067.
| Kinase experiment [1]: | |
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Binding assays |
Kinases were activated by preincubating the enzyme (2.7 μmol/L final concentration) in 50 mmol/L HEPES (pH 7.5), 10 mmol/L MgCl2, 0.1 mg/mL bovine serum albumin, and 2 mmol/L ATP. Compounds were diluted in DMSO and dispensed into the assay plates (100 nL/well). Kinase reactions contained (in 10 μL volume) 50 mmol/L HEPES (pH 7.5), 3 mmol/L DTT, 0.1 mg/mL bovine serum albumin, 1 mmol/L CHAPS, 10 mmol/L MgCl2, 10 μmol/L ATP, 500 nmol/L substrate peptide (biotin-aminohexyl-AEEEEYMMMMAKKKK-NH2; QPC), and 0.5 nmol/L activated enzyme. Reactions were stopped after 1 h at room temperature with 33 μmol/L EDTA. Peptide phosphorylation was measured by time-resolved fluorescence resonance energy transfer with 7 nmol/L streptavidin-Surelight allophycocyanin and 1 nmol/L europium-conjugated phosphotyrosine antibodies. Plates were read in a Victor X5 or ViewLux 1430 ultra HTS microplate imager. |
| Cell experiment [1]: | |
|
Cell lines |
NIH-3T3 cells that overexpress human IGF-IR [NIH-3T3-hIGF-IR (NIH-3T3/LISN)] and IR (NIH-3T3-hIR) |
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Preparation method |
The solubility of this compound in DMSO is >42.6mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
72 h |
|
Applications |
In the NIH-3T3/LISN and NIH-3T3-hIR cells, GSK1904529A potently inhibited phosphorylation of IGF-IR and IR with the IC50 of 22 ± 8 nmol/L and 19 ± 8 nmol/L, respectively. GSK1904529A suppressed cell proliferation in a variety of tumor cells with the IC50 values of 81, 35, 43, 124, 137 and 68 nM for NCI-H929, TC-71, SK-N-MC, COLO 205, MCF7 and PREC, respectively. In COLO 205, MCF-7, and NCI-H929 cells, GSK1904529A resulted in cell accumulation in G1 and decrease in S and G2-M phases. |
| Animal experiment [1]: | |
|
Animal models |
Female athymic nu/nu CD-1 mice bearing NIH-3T3/LISN, COLO 205, HT29, and BxPC3 cells |
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Dosage form |
Oral administration, 30 mg/kg, once or twice daily for 21 d |
|
Application |
In NIH-3T3/LISN tumor-bearing mice, GSK1904529A (oral, 30 mg/kg, twice-daily) inhibited 98% tumor growth. In COLO 205 xenografts mice, GSK1904529A (oral, 30 mg/kg, once daily) inhibited 75% tumor growth. Among HT29 and BxPC3 xenografts, GSK1904529A produced moderate tumor growth inhibition with no side effects at a dose of 30 mg/kg. |
|
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. |
|
References: [1]. Sabbatini P, Rowand J L, Groy A, et al. Antitumor activity of GSK1904529A, a small-molecule inhibitor of the insulin-like growth factor-I receptor tyrosine kinase. Clinical Cancer Research, 2009, 15(9): 3058-3067. |
|
| Cas No. | 1089283-49-7 | SDF | |
| المرادفات | GSK4529 | ||
| Chemical Name | N-(2,6-difluorophenyl)-5-[3-[2-[5-ethyl-2-methoxy-4-[4-(4-methylsulfonylpiperazin-1-yl)piperidin-1-yl]anilino]pyrimidin-4-yl]imidazo[1,2-a]pyridin-2-yl]-2-methoxybenzamide | ||
| Canonical SMILES | CCC1=CC(=C(C=C1N2CCC(CC2)N3CCN(CC3)S(=O)(=O)C)OC)NC4=NC=CC(=N4)C5=C(N=C6N5C=CC=C6)C7=CC(=C(C=C7)OC)C(=O)NC8=C(C=CC=C8F)F | ||
| Formula | C44H47F2N9O5S | M.Wt | 851.96 |
| الذوبان | ≥ 42.6mg/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. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.1738 mL | 5.8688 mL | 11.7376 mL |
| 5 mM | 0.2348 mL | 1.1738 mL | 2.3475 mL |
| 10 mM | 0.1174 mL | 0.5869 mL | 1.1738 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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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
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 21 reference(s) in Google Scholar.)
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