PF-562271 is a reversible, ATP-competitive inhibitor of focal adhesion kinase (FAK) and the related kinase PYK2. EBC-221077 corresponds to the besylate salt, CAS 939791-38-5.
Application of PF-562271
Researchers use this compound to investigate how FAK inhibition affects cell migration, invasion and anchorage-independent growth. Pairing phosphorylation measurements with these functional assays helps establish whether reduced kinase signaling accompanies a change in cell behavior. FAK-null or kinase-dead controls help distinguish effects of catalytic inhibition from other activities. Also known as PF-00562271, the compound can serve as a benchmark for medicinal chemists evaluating new FAK inhibitors under matched assay conditions.
In Vitro
In recombinant enzyme assays, the PF-562271 FAK inhibitor showed IC50 values of 1.5 nM for FAK and 14 nM for PYK2. An inducible cellular phospho-FAK assay gave an IC50 of 5 nM.
Serrels and colleagues found that treatment with the PF-562271 focal adhesion kinase inhibitor reduced migration in squamous carcinoma cells. However, monolayer proliferation was inhibited at similar micromolar concentrations in cells expressing wild-type FAK, lacking FAK or expressing kinase-deficient FAK. Growth inhibition in this setting therefore cannot be attributed solely to FAK catalytic blockade.
In Vivo
Following oral administration, the FAK inhibitor PF-00562271 reduced tumor FAK phosphorylation in mice, with a calculated EC50 of 93 ng/mL based on total drug concentration. Maximum tumor growth inhibition of 78–94% was reported across PC-3M, BT474, BxPc3 and LoVo xenografts. These findings provide model-specific evidence; response depends on dose and exposure.
Biochemical and Physiological Actions
The PF-562271 chemical structure contains a trifluoromethyl-substituted diaminopyrimidine core linked to oxindole and pyridine groups.
FAK integrates signals from integrins and growth factor receptors. Autophosphorylation at Tyr397 creates a Src-binding site that supports signaling involved in motility and survival. The inhibitor reduces this phosphorylation.
The PF-562271 molecular structure has been characterized in complex with the FAK kinase domain, providing a structural basis for ATP-site inhibition. Activity against PYK2 and some CDKs means that cellular effects require interpretation beyond FAK alone.
Features and Benefits of PF-562271
Published enzyme, cell and animal studies provide reference data across different stages of preclinical research. Comparisons still require matching assay conditions and endpoints.
The PF-562271 molecular weight is 665.66 g/mol for the besylate, compared with approximately 507.5 g/mol for the free base. Check the PF-562271 structure and salt form before calculating stock concentrations: using the free-base value for weighed besylate overestimates molarity by about 31%.
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