GSK1904529A (GSK-4529; GSK-1904529A; GSK 4529)

Alias: GSK 1904529a; GSK-1904529a; GSK 4529; GSK4529; GSK-4529; GSK1904529a
Cat No.:V0623 Purity: ≥98%
GSK1904529A (also known as GSK-4529; GSK-1904529A; GSK 4529) is a novel, potent and selective inhibitor of IGF-1R (insulin-like growth factor-1 receptor) and IR (insulin receptor) with potential anticancer activity.
GSK1904529A (GSK-4529; GSK-1904529A; GSK 4529) Chemical Structure CAS No.: 1089283-49-7
Product category: IFG-1R
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

GSK1904529A (also known as GSK-4529; GSK-1904529A; GSK 4529) is a novel, potent and selective inhibitor of IGF-1R (insulin-like growth factor-1 receptor) and IR (insulin receptor) with potential anticancer activity. It exhibits >100-fold higher selectivity for IGF-1R/InsR than Akt1/2, Aurora A/B, B-Raf, CDK2, EGFR, and so on. In cell-free assays, it inhibits IGF-1R and IR with IC50s of 27 nM and 25 nM, respectively. In tumor-bearing NIH-3T3/LISN mice, GSK1904529A demonstrates exceptional high in vivo antitumor efficacy.

Biological Activity I Assay Protocols (From Reference)
Targets
IGF-1R (IC50 = 27 nM); IR (IC50 = 25 nM)
ln Vitro

GSK1904529A is an ATP-competitive, reversible inhibitor with 1.6 nM and 1.3 nM, respectively, for enzyme-inhibitor binding values against IGF-1R and IR. At concentrations greater than 0.01 μM, GSK1904529A strongly inhibits the ligand-induced phosphorylation of IGF-1R and IR, subsequently obstructing downstream signaling (AKT, IRS-1, and ERK). NIH-3T3/LISN, TC-71, SK-N-MC, SK-ES, and RD-ES cells are all potently inhibited by GSK1904529A, with IC50 values of 60 nM, 35 nM, 43 nM, 61 nM, and 62 nM, respectively. Other Ewing's sarcoma and multiple myeloma cell lines, such as NCI-H929, MOLP-8, LP-1, and KMS-12-BM, are also inhibited by GSK1904529A. GSK1904529A is sensitive to the cell lines COLO 205, MCF-7, and NCI-H929; these lines experience cell cycle arrest at the G1 phase.[1]

ln Vivo
GSK1904529A shows that a dose of 30 mg/kg (orally, twice daily) in tumor-bearing NIH-3T3/LISN mice results in 98% tumor growth inhibition, and a dose of 75 mg/kg (once daily) in xenograft mice COLO 205. At a dose of 30 mg/kg, GSK1904529A inhibits tumor growth in HT29 and BxPC3 xenografts moderately and without causing any side effects. GSK1904529A, meanwhile, has very little effect on blood glucose levels. GSK1904529A fully prevents IGF-1R phosphorylation at a blood concentration of about 3.5 μM. Prostate, colon, breast, pancreatic, ovarian, and sarcomas are among the IGF-1R-dependent tumors for which GSK1904529A has been linked to treatment.[1]
Enzyme Assay
In DMSO stock solution, GSK1904529A is dissolved at a concentration of 10 mM. To calculate IC50, proteins tagged with glutathione S-transferase and encoding the intracellular domain of IGF-1R (amino acids 957–1367) and IR (amino acids 979–1382) are expressed by baculoviruses. The process of preincubating the enzyme (at a final concentration of 2.7 μM) in 50 mM HEPES (pH 7.5), 10 mM MgCl2, 0.1 mg/mL bovine serum albumin, and 2 mM ATP activates kinases. Distilled in DMSO, 100 nL/well of GSK1904529A is poured into the assay plates. Included kinase reactions (10 μL) The following ingredients are included: 500 nM substrate peptide (biotin-aminohexylAEEEEYMMMMAKKKK-NH2; QPC), 3 mM DTT, 0.1 mg/mL bovine serum albumin, 1 mM CHAPS, 10 mM MgCl2, 10 μM ATP, and 0.5 nM activated enzyme. After an hour at room temperature with 33 μM EDTA, reactions are terminated. Time-resolved fluorescence resonance energy transfer using 7 nM streptavidin Surelight allophycocyanin and 1 nM europium-conjugated phosphotyrosine antibodies is used to measure phosphorylation of peptides. A multilabel reader reads plates.
Cell Assay
In 96-well plates, cells are seeded, allowed to grow overnight at 37 °C, and then exposed to different concentrations of GSK1904529A for a full 72 hours. On collagen-coated 96-well tissue culture plates, cells are seeded for the NIH-3T3/LISN and given a 24-hour window to adhere. Serum-free medium is used in place of the tissue culture medium, and the cells are treated with either DMSO or GSK1904529A for two hours. Following the addition of IGF-I (30 ng/mL), the cells are incubated for 72 hours at 37 °C. The CellTiter-Glo Luminescent Cell Viability Assay is used to quantify the proliferation of cells. The IC50 values are established.
Animal Protocol
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
~30 mg/kg
Orally administered
References

[1]. Clin Cancer Res . 2009 May 1;15(9):3058-67.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C44H47F2N9O5S
Molecular Weight
851.96
Exact Mass
851.34
Elemental Analysis
C, 62.03; H, 5.56; F, 4.46; N, 14.80; O, 9.39; S, 3.76
CAS #
1089283-49-7
Appearance
Solid powder
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
InChi Key
MOSKATHMXWSZTQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C44H47F2N9O5S/c1-5-28-26-35(38(60-3)27-36(28)53-19-15-30(16-20-53)52-21-23-54(24-22-52)61(4,57)58)49-44-47-17-14-34(48-44)42-40(50-39-11-6-7-18-55(39)42)29-12-13-37(59-2)31(25-29)43(56)51-41-32(45)9-8-10-33(41)46/h6-14,17-18,25-27,30H,5,15-16,19-24H2,1-4H3,(H,51,56)(H,47,48,49)
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
Synonyms
GSK 1904529a; GSK-1904529a; GSK 4529; GSK4529; GSK-4529; GSK1904529a
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~124 mg/mL (~145.5 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Preparing Stock Solutions 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

*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.

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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.

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Biological Data
  • GSK1904529A

  • GSK1904529A

    Effect of GSK1904529A on IR phosphorylation and glucose metabolism. Clin Cancer Res. 2009 May 1;15(9):3058-67.

  • GSK1904529A

    Effect of GSK1904529A on IGF-IR phosphorylation in vivo. Clin Cancer Res. 2009 May 1;15(9):3058-67.

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