GSK1904529A

Catalog No.S1093 Synonyms: GSK 4529

For research use only.

GSK1904529A (GSK 4529) is a selective inhibitor of IGF-1R and IR with IC50 of 27 nM and 25 nM in cell-free assays, >100-fold more selective for IGF-1R/InsR than Akt1/2, Aurora A/B,B-Raf, CDK2, EGFR etc.

GSK1904529A Chemical Structure

CAS No. 1089283-49-7

Selleck's GSK1904529A has been cited by 20 publications

Purity & Quality Control

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Biological Activity

Description GSK1904529A (GSK 4529) is a selective inhibitor of IGF-1R and IR with IC50 of 27 nM and 25 nM in cell-free assays, >100-fold more selective for IGF-1R/InsR than Akt1/2, Aurora A/B,B-Raf, CDK2, EGFR etc.
Targets
Insulin Receptor [1]
(Cell-free assay)
IGF-1R [1]
(Cell-free assay)
25 nM 27 nM
In vitro

GSK1904529A is a reversible, ATP-competitive inhibitor and has enzyme-inhibitor binding values against IGF-1R and IR with Ki of 1.6 nM and 1.3 nM, respectively. GSK1904529A potently inhibits the ligand-induced phosphorylation of IGF-1R and IR at concentrations above 0.01 μM, followed by blocking downstream signaling (AKT, IRS-1, and ERK). GSK1904529A potently inhibits NIH-3T3/LISN, TC-71, SK-N-MC, SK-ES RD-ES cells with IC50 of 60 nM, 35 nM, 43 nM, 61 nM and 62 nM, respectively. GSK1904529A also inhibits other multiple myeloma and Ewing's sarcoma cell lines including NCI-H929, MOLP-8, LP-1 and KMS-12-BM etc. GSK1904529A induces cell cycle arrest at the G1 phase in cell lines COLO 205, MCF-7, and NCI-H929, which are sensitive to GK1904529A. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NIH3T3 cells NEHsW5BHfW6ldHnvckBie3OjeR?= M2XFfGlvcGmkaYTpc44hd2ZiaIXtZY4hcW6|dXzpckBz\WOncITvdkBifXSxcHjvd5Bpd3K7bHH0bY9vKGmwIITyZY5{\mWldHXkJI1wfXOnIF7JTFNVOyClZXzsd{whUUN3ME2xPUBvVQ>? MoTtNVkyODFzNEO=
human TC71 cells MmXNVJJwdGmoZYLheIlwdiCjc4PhfS=> MXO3NkBp MnvtRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCWQ{exJINmdGy|IHHmeIVzKDd{IHjyd{BjgSCFZXzseIl1\XJiYYPzZZktKEmFNUC9N|Uhdk1? Mn7xNVkyODFzNEO=
human SK-ES cells NYDJW3ZFWHKxbHnm[ZJifGmxbjDhd5NigQ>? M1jOUVczKGh? M{f1bmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1utSXMh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IFPlcIx1cXSncjDhd5NigSxiSVO1NF03OSCwTR?= MmTHNVkyODFzNEO=
human NCI-H929 cells NVLBWXNuWHKxbHnm[ZJifGmxbjDhd5NigQ>? M2S3T|czKGh? M3Ow[mFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTlPJMWg6OjliY3XscJMh[W[2ZYKgO|IhcHK|IHL5JGNmdGy2aYTldkBie3OjeTygTWM2OD16MTDuUS=> MXuxPVExOTF2Mx?=
human LP-1 cells NFHxfHZRem:uaX\ldoF1cW:wIHHzd4F6 MlLIO|IhcA>? NE\FXoVCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFzQMVEh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IFPlcIx1cXSncjDhd5NigSxiSVO1NF0yODRibl2= MonnNVkyODFzNEO=
human COLO205 cells NGW1XFdRem:uaX\ldoF1cW:wIHHzd4F6 MnHSO|IhcA>? NGDVfHVCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFPPUG8zODViY3XscJMh[W[2ZYKgO|IhcHK|IHL5JGNmdGy2aYTldkBie3OjeTygTWM2OD1zMkSgcm0> MknjNVkyODFzNEO=
Assay
Methods Test Index PMID
Growth inhibition assay Cell number 28572530
In vivo GSK1904529A indicates 98% tumor growth inhibition in NIH-3T3/LISN tumor-bearing mice at a dose of 30 mg/kg (orally, twice-daily) and 75% in COLO 205 xenografts mice (once daily). Among HT29 and BxPC3 xenografts, GSK1904529A produces moderate tumor growth inhibition with no side effects at a dose of 30 mg/kg. Meanwhile, GSK1904529A shows minimal effects on blood glucose levels. GSK1904529A (~3.5 μM in blood) completely inhibits IGF-1R phosphorylation. GSK1904529A has been implicated in treatment of various IGF-1R-dependent tumors including prostate, colon, breast, pancreatic, ovarian, and sarcomas. [1]

Protocol (from reference)

Kinase Assay:

[1]

  • Kinase assays:

    GSK1904529A is dissolved in DMSO as stock solution at 10 mM. Baculovirus-expressed glutathione S-transferase-tagged proteins encoding the intracellular domain of IGF-1R (amino acids 957-1367) and IR (amino acids 979-1382) are used for determination of IC50. Kinases are activated by preincubating the enzyme (2.7 μM final concentration) in 50 mM HEPES (pH 7.5), 10 mM MgCl2, 0.1mg/mL bovine serum albumin, and 2 mM ATP. GSK1904529A is diluted in DMSO and dispensed into the assay plates (100 nL/well). Kinase reactions contained (in 10 μL) 50 mM HEPES (pH 7.5), 3 mM DTT, 0.1mg/mL bovine serum albumin, 1mM CHAPS, 10 mM MgCl2, 10 μM ATP, 500 nM substrate peptide (biotin-aminohexylAEEEEYMMMMAKKKK-NH2; QPC), and 0.5 nM activated enzyme. Reactions are stopped after 1 hour at room temperature with 33 μM EDTA. Peptide phosphorylation is measured by time-resolved fluorescence resonance energy transfer with 7 nM streptavidin Surelight allophycocyanin and 1nM europium-conjugated phosphotyrosine antibodies. Plates are read in a multilabel reader.

Cell Research:

[1]

  • Cell lines: Tumor cell lines including multiple myeloma, ewing's sarcoma, askin's tumor, colon, breast, anaplastic large cell lymphoma, lung, cervix, head and neck, prostate and ovary.
  • Concentrations: ~ 100 μM, stocked in DMSO at 10 mM.
  • Incubation Time: 72 hours
  • Method:

    Cells are seeded in 96-well plates and incubated overnight at 37 °C, and treated with various concentrations of GSK1904529A for 72 hours. For the NIH-3T3/LISN, cells are seeded on collagen-coated 96-well tissue culture plates and allowed to adhere for 24 hours. The tissue culture medium is replaced with serum-free medium and the cells are treated with DMSO or GSK1904529A for 2 hours. IGF-I (30 ng/mL) is added and the cells are incubated at 37 °C for 72 hours. Cell proliferation is quantified using the CellTiter-Glo Luminescent Cell Viability Assay. IC50 values are determined.

  • (Only for Reference)
Animal Research:

[1]

  • Animal Models: NIH-3T3/LISN, COLO 205, HT29, and BxPC3 cells are implanted s.c. into the right flank of 8- to 10-wk-old female nu/nu CD-1athymic mice.
  • Dosages: ~30 mg/kg
  • Administration: Orally administered
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 124 mg/mL
(145.54 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 851.96
Formula

C44H47F2N9O5S

CAS No. 1089283-49-7
Storage 3 years -20°C powder
2 years -80°C in solvent
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

In vivo Formulation Calculator (Clear solution)

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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.
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Molarity Calculator

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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