A selective inhibitor of IGF-1R
AG1024 is an inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR) that specifically inhibits autophosphorylation of IGF-1R and IR with IC50 values of 7μM and 57 μm, respectively [1].
AG1024 has shown to inhibit IGF-1- and insulin-stimulated cellular proliferation in NIH-3T3 mouse fibroblast cells with IC50 values of 0.4μM and 0.1μM, respectively. Additionally, AG1024 shows to block tyrosine kinase activity towards exogenous substrates (TKA) with IC50 values of 18μM and 80μM [1].
AG1024 has been reported to block receptor tyrosine kinase activity, resulting in abolishment of MAPK and Akt pathways and inhibition of cell growth. Moreover, studies showed that AG1024 concentration-dependently inhibited E2 stimulation in MCF-7:PF cells [2].
参考文献:
[1] Párrizas M1,?Gazit A,?Levitzki A,?Wertheimer E,?LeRoith D. Specific inhibition of insulin-like growth factor-1 and insulin receptor tyrosine kinase activity and biological function by tyrphostins. Endocrinology.?1997 Apr;138(4):1427-33.
[2] Fan P1,?Agboke FA1,?McDaniel RE1,?Sweeney EE1,?Zou X1,?Creswell K1,?Jordan VC2.Inhibition of c-Src blocks oestrogen-induced apoptosis and restores oestrogen-stimulated growth in long-term oestrogen-deprived breast cancer cells. Eur J Cancer.?2014 Jan; 50(2):457-68.
| Cell experiment: [1] | |
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Cell lines |
MCF-7 |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
10 nM, 5 days for cell proliferation inhibition 10 nM, 48 hours for apoptosis induction |
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Applications |
The Tyrphostin AG-1024 induced a marked decrease of cell proliferation in a time-dependent manner. It also potently induced cell apoptosis with a 20.1 % of apoptotic cells. |
| Animal experiment : [2] | |
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Animal models |
Female nude mice implanted with Ba/F3-p210 cells |
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Dosage form |
Intraperitoneal injection, 30 μg in100 μl, once per day for 10 days |
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Applications |
After injection with Ba/F3-p210 cells (Bcr-Abl expressing cells), nude mice were injected after 6 days with PBS 0.1 ml (control) or Tyrphostin AG1024 30 μg/100 μl (1 μl of 980 μM). The growth of the Ba/F3-p210 xenografts was significantly delayed when mice were treated with Tyrphostin AG1024. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1] Wen B, Deutsch E, Marangoni E, et al. Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells. British journal of cancer, 2001, 85(12): 2017. [2] Deutsch E, Maggiorella L, Wen B, et al. Tyrosine kinase inhibitor AG1024 exerts antileukaemic effects on STI571-resistant Bcr-Abl expressing cells and decreases AKT phosphorylation. British journal of cancer, 2004, 91(9): 1735-1741. | |
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