AG-213

AG-213 is an inhibitor of protein tyrosine kinases (PTKs) and epidermal growth factor (EGF) receptor kinase [1,2].

Protein tyrosine kinases (PTKs) have been involved in regulating cell proliferation, cell differentiation, and signaling processes in the immune system. Dysfunction of protein tyrosine kinases result in inflammatory responses and diseases including cancer, atherosclerosis, and psoriasis [3]. The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein. Activation of EGFR results in autophosphorylation of receptor tyrosine kinase and has been involved in regulating cellular proliferation, differentiation, and survival. Overexpression of EGFR has been identified in a variety of tumor cell lines and has been associated with poor prognosis and decreased survival [4].

Administration of AG 213(100 μM) interfered with HUVEC focal adhesion and stress fiber formation. Pretreatment of monolayers with AG 213 (25, 50, and 75 μM) produced partial and incremental inhibition of HUVEC migration. In HUVEC, treatment with tyrphostin AG 213 (25 and 50 μM) demonstrated partial inhibition of stress fiber assembly compared with cells treated with 100 μM AG 213 [1]. AG 213 inhibited adhesion-associated tyrosine phosphorylation of pp125FAK activity in HUVEC [1]. AG-213 inhibited the activity of epidermal growth factor (EGF) receptor kinase with an IC50 value of 2.4 μM in the human epidermoid carcinoma cell line A431 [2].

References:
[1] Romer L H, McLean N, Turner C E, et al.  Tyrosine kinase activity, cytoskeletal organization, and motility in human vascular endothelial cells[J]. Molecular Biology of the Cell, 1994, 5(3): 349-361.
[2] Gazit A, Yaish P, Gilon C, et al.  Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors[J]. Journal of medicinal chemistry, 1989, 32(10): 2344-2352.
[3] Levitzki A, Gazit A.  Tyrosine kinase inhibition: an approach to drug development[J]. Science, 1995, 267(5205): 1782.
[4] Herbst R S.  Review of epidermal growth factor receptor biology[J]. International Journal of Radiation Oncology Biology Physics, 2004, 59(2): S21-S26.