GSK1904529A 是一种有效的，选择性的，具有口服活性和 ATP 竞争性的胰岛素样生长因子 1 受体 (IGF-1R) 和胰岛素受体 (IR) 抑制剂，IC50值分别为 27 和 25 nM。GSK1904529A 在其他 45 种丝氨酸/苏氨酸和酪氨酸激酶中显示出较弱的活性 (IC50>1 μM)。GSK1904529A 具有抗肿瘤活性。
| 生物活性 | GSK1904529A is a potent, selective, orally active, and ATP-competitive inhibitor ofinsulin-like growth factor-1 receptor (IGF-1R)andinsulin receptor(IR), withIC50s of 27 and 25 nM, respectively. GSK1904529A shows poor activity (IC50>1 μM) in 45 other serine/threonine and tyrosine kinases. GSK1904529A exhibits anti-tumor activity[1][2]. |
| IC50& Target | IC50: 27 nM (IGF-1R), 25 nM (IR)[1] |
体外研究
(In Vitro) | GSK1904529A displays high affinities for IGF-1R and IR, with Kis of 1.6 and 1.3 nM, respectively[1].
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[1].
GSK1904529A (0.03-3 μM; 24 and 48 h) arrests cells at the G1 phase of the cell cycle[1].
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[1].
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[1].
Cell Cycle Analysis[1] | 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[1] | 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. |
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体内研究
(In Vivo) | GSK1904529A (30 mg/kg; p.o. once or twice daily for 21 d) has antitumor activity in mice[1].
GSK1904529A (1-30 mg/kg; a single p.o.) decreases IGF-I-induced IGF-IR phosphorylation in a dose-dependent manner in mice[1].
GSK1904529A (30 mg/kg; p.o. once or twice daily for 21 d) has no significant alterations in the blood glucose levels in mice[1].
| Animal Model: | Female athymicnu/nuCD-1 mice are bring NIH-3T3/LISN tumor[1] | | 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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 50 mg/mL(58.69 mM;Need ultrasonic) 配制储备液 | 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 |
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