GSK1904529A

SKU: orb1227009

Description

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

Key Properties

• CAS Number: 1089283-49-7
• MW: 851.96
• Purity: >98% (HPLC)
• Formula: C₄₄H₄₇F₂N₉O₅S
• SMILES: O=C(NC1=C(F)C=CC=C1F)C2=CC(C3=C(C4=NC(NC5=CC(CC)=C(N6CCC(N7CCN(S(=O)(C)=O)CC7)CC6)C=C5OC)=NC=C4)N8C=CC=CC8=N3)=CC=C2OC
• Target: IGF-1R
• Solubility: DMSO:124 mg/mL (145.54 mM); Ethanol:<1 mg/mL (<1 mM); Water：<1 mg/mL (<1 mM)

Bioactivity

• In Vivo:
  GSK1904529A (30 mg/kg; p.o. once or twice daily for 21 d) has antitumor activity in mice. GSK1904529A (1-30 mg/kg; a single p.o.) decreases IGF-I-induced IGF-IR phosphorylation in a dose-dependent manner in mice. GSK1904529A (30 mg/kg; p.o. once or twice daily for 21 d) has no significant alterations in the blood glucose levels in mice. Animal model: Female athymic nu/nu CD-1 mice are bring NIH-3T3/LISN tumor. Dosage: 30 mg/kg. Administration: p.o. once or twice daily for 21 d. Result: Resulted in 56% (once daily) and 98% (twice daily) inhibition of tumor growth. No significant decrease in body weight on the once daily schedule. Observed 11-13% of body weight loss, and recovered to near baseline 6 days after the cessation of treatment in twice-daily group.
• In Vitro:
  GSK1904529A displays high affinities for IGF-1R and IR, with Kis of 1.6 and 1.3 nM, respectively. GSK1904529A (72 h) inhibits tumor cells proliferation with IC50s ranges from 35 nM to >30 μM, and Ewing's sarcoma and multiple myeloma cell lines are greatest sensitive. GSK1904529A (0.03-3 μM; 24 and 48 h) arrests cells at the G1 phase of the cell cycle. GSK1904529A (2 h) inhibits phosphorylation of IGF-IR and IR with IC50s of 22 and 19 nM in NIH-3T3/LISN and NIH-3T3-hIR cells, respectively. GSK1904529A (0.01-3 μM; 4 h) blocks the major downstream signal transduction pathways mediated by IGF-IR and IR in NIH-3T3/LISN and NIH-3T3-hIR cells. Cell Cycle Analysis Cell line: COLO 205, MCF-7, and NCI-H929 cells. Concentration: 0, 0.03, 0.1, 0.3, 1, 3 μM Incubation time: 24 and 48 hours. Result: Increased the accumulation in G1 and decreased accumulation in S and G2-M phases of the cell cycle. Western blot analysis. Cell line: NIH-3T3/LISN and NIH-3T3-hIR cells. Concentration: 0.01, 0.03, 0.1, 0.3, 1, 3 μM Incubation time: 4 hours. Result: Inhibited the ligand-induced phosphorylation of IGF-IR and IR at concentrations >0.01 μM. Decreased the phosphorylation of AKT, IRS-1, and ERK.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GSK-4529 | GSK1904529a | GSK 1904529 | GSK-1904529a

Quick Database Links

Gene Symbol

IGF-1R