GSK1904529A

SKU: orb1689845

Description

GSK1904529A is a potent dual inhibitor of IGF-1R and IR with IC50 values of 27 nM and 25 nM, respectively. This small molecule is a valuable research tool for studying insulin/IGF-1 signaling pathways in cancer and metabolic disease research, with demonstrated utility in both in vitro and in vivo experimental models.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 1089283-49-7
• MW: 851.96
• Purity: 99.76% (May vary between batches)
• Formula: C₄₄H₄₇F₂N₉O₅S
• SMILES: CCc1cc(Nc2nccc(n2)-c2c(nc3ccccn23)-c2ccc(OC)c(c2)C(=O)Nc2c(F)cccc2F)c(OC)cc1N1CCC(CC1)N1CCN(CC1)S(C)(=O)=O
• Target: Syk,VEGFR,Raf,IGF-1R,Apoptosis
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (4.7 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:16.11 mg/mL (18.91 mM)

Bioactivity

• Target IC50:
  Insulin receptor:25 nM|IGF-1R:27 nM
• 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.
• 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.
• Cell Research:
  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.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

B-Raf (V600E), Apoptosis, anti-tumor, inhibit, Inhibitor, GSK4529, GSK-4529, GSK1904529A, GSK-1904529A, GSK 4529, IGF-1R, IGF1R, insulin, Insulin Receptor, Syk, VEGFR2

Compound Identifiers

PubChem CID

25124816