Cancer cells are characterized by the ability to grow in an anchorage-independent manner.The activity of the nonreceptor tyrosine kinase,focal adhesion kinase (FAK),is thought to contribute to this phenotype.Recent studies show FAK is positively correlated with clinical cancer invasiveness and metastasis.FAK inhibition has dual mechanisms (anti-tumor and anti-angiogenic).PF-562,271 is a potent,ATP-competitive,reversible inhibitor of FAK catalytic activity with an IC50 of 1.5 nmol/L,and in vivo activity showed tumor regressions in 5/7 xenograft models.PF-562,271 not only possessed anti tumor potency both in vitro and in vivo,it also has a desirable molecular properties and PK profile.PF-562,271 was predicted to have low to moderate clearance (Cl) and volume of distribution (Vdss) and high oral bioavailability using in vitro human reagents and in vivo animal allometry scaling.The major clearance pathway was predicted as hepatic metabolic only and CYP3A was the major isozyme responsible for the metabolism of PF-562,271.Furthermore,PF-562271 showed mechanism based-inhibition against CYP3A based on the prediction from human in vitro reagents and Simcyp software.Based on the human PK prediction and efficacy models,human does was predicted in the range of 36-74 mg BID for 70 kg man.Finally,clinical PK and DDI data will be presented to compare to those in vitro prediction and model simulation.