tcsc2663 PF-562271 (besylate)

PF-562271 (besylate) is a potent, ATP-competitive, reversible inhibitor of FAK and Pyk2 kinase with IC₅₀ of 1.5 nM and 13 nM, and has > 100-fold selectivity against other protein kinases, except for some CDKs.

IC50 & Target: IC50: 1.5 nM (FAK), 13 nM (Pyk2)

In Vitro: PF-562,271 is a 30- to 120-nM (15.2 to 60.1 ng/mL) inhibitor of cdk2/E, cdk5/p35, cdk1/B, and cdk3/E in recombinant enzyme assays^[1]. PF-562,271 blocks bFGF-stimulated blood vessel angiogenesis as performed in chicken chorioallantoic membrane assays^[2]. Treatment of cells with PF-562,271 or knock-down of FAK by siRNA is observed to increase cell-cell adhesion strength^[3].

In Vivo: PF-562,271 (33 mg/kg, p.o.) inhibits FAK phosphorylation in tumors in a dose- and time-dependent manner in tumor-bearing mice. FAK phosphorylation inhibition relative to total blood concentration of PF-562,271 results in a calculated EC₅₀ of 93 ng/mL. PF-562,271 (25 mg/kg, p.o.) induces apoptosis 2-fold greater in treated tumors compared with vehicle-treated control tumors on day 3^[1]. PF-562,271 (33 mg/kg, p.o.) and dasatinib extensively inhibit the movement of tumor cells in the animals. Inhibition of FAK kinase activity following treatment with PF-562,271 results in altered E-cadherin dynamics in vivo^[3].