Focal adhesion kinase (FAK) is a member of a family of non-receptor protein-tyrosine kinases. The FAK4 family kinases (which include FAK and Pyk2) regulate integrin and growth factor signaling pathways involved in cell migration, proliferation, survival. Besides, FAK expression is increased in many cancers, including breast and prostate cancer. Moreover, there are integrin engagement and clustering stimulates FAK phosphorylation on Tyr397. And they create a high-affinity binding site for Src and Src family kinases. In addition to FAK catalytic activity, FAK also functions as a scaffold to organize structural and signaling proteins within focal adhesions. Furthermore, the importance of FAK as a regulator of normal cellular function is underscored by the number of cancers reported to have alterations in FAK expression and/or activity. Additionally, alterations in FAK expression and/or activity have related to tumorigenesis and increased metastatic potential. PF-573228 is a potent and selective FAK inhibitor.

PF-573228 is a potent and selective FAK inhibitor with IC50 of 4 nM for the purified recombinant catalytic fragment of FAK. In cultured cells, PF-573228 inhibited FAK phosphorylation on Tyr(397) with an IC50 of 30-100 nM. Meanwhile, the treatment of cells with PF-573228 significantly decreased FAK Tyr(397) phosphorylation failed to inhibit cell growth or induce apoptosis. Nonetheless, PF-573228 serves as a useful tool to dissect the functions of FAK in integrin-dependent signaling pathways in normal and cancer cells. Finally, this forms the basis for the generation of compounds amenable for preclinical and patient trials. All in all, PF-573228 is a potent and selective FAK inhibitor.



Slack-Davis JK, et al. J Biol Chem. 2007 May 18;282(20):14845-52.