AG-1024 Inhibitor CAS No. 65678-07-1

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Chemical Characteristic

Product Name	AG-1024
Synonyms	AG-1024; Tyrphostin
CAS No.	65678-07-1
Molecular Weight	305.17
Formula	C₁₄H₁₃BrN₂O
Chemical Name	2-(3-bromo-5-tert-butyl-4-hydroxybenzylidene)malononitrile
Smiles	C(#N)C(=Cc1cc(c(c(c1)C(C)(C)C)O)Br)C#N
Chemical Structure

Biological activities

AG1024 is an IGF-1R inhibitor. AG1024 inhibits insulin-like growth factor(IGF)-1R with an IC50 of about 400 nM. AG1024 has anti-tumor activity. IGF-1 plays an important growth-promoting effect by activating the PI3K/Akt signaling pathway, inhibiting apoptotic pathways and mediating mitogenic actions. AG1024 has stimulatory effects on proliferation, radiosensitivity, and radiation-induced cell apoptosis in a human breast cancer cell line MCF-7. Exposure to AG1024 inhibits proliferation and induces apoptosis in a time-dependent manner, and the degree of growth inhibition for IC20 plus irradiation (4 Gy) is up to 50% compared to the control.^[1] Moreover, AG1024 inhibits the mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK) pathway and restores pRb tumor suppressive function. In addition, in vivo, AG1024-induces apoptosis is associated with a down-regulation of expression of phospho-Akt1, increased expression of Bax, p53 and p21, and a decreased expression of bcl-2 expression. AG1024 also inhibits the MAPK/ERK pathway and restores pRb tumor suppressive function.^[2]

Protocols

In vitro, AG1024 is dissolved in DMSO.^[3]

References

[1] Wen B, et al. Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells. British journal of cancer. 2001, 85(12): 2017. [2] Willebrand MV, et al. The Tyrphostin AG1024 Accelerates the Degradation of Phosphorylated Forms of Retinoblastoma Protein (pRb) and Restores pRb Tumor Suppressive Function in Melanoma Cells 1. Cancer Res. 2003, 63: 1420 [3] Chakraborty AK, et al. Co-targeting the insulin-like growth factor I receptor enhances growth-inhibitory and pro-apoptotic effects of anti-estrogens in human breast cancer cell lines. Breast Cancer Res Treat. 2010, 120(2): 327-335.

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