PF-00562271

PF-00562271 is the benzenesulfonate salt of PF-562271, which is a potent, ATP-competitive, reversible inhibitor of FAK with IC50 of 1.5 nM, ~10-fold less potent for Pyk2 than FAK and >100-fold selectivity against other protein kinases, except for some CDKs. Phase 1. (In Vitro) :PF-562271 (VS-6062) besylate 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. PF-562,271 blocks bFGF-stimulated blood vessel angiogenesis as performed in chicken chorioallantoic membrane assays. Treatment of cells with PF-562,271 or knock-down of FAK by siRNA is observed to increase cell-cell adhesion strength. (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. 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.

939791-38-5

>98% (HPLC)

DMSO:14 mg/mL warmed (21.03 mM) ; Ethanol:<1 mg/mL (<1 mM) ; Water:<1 mg/mL (<1 mM)

OS (=O) (=O) C1=CC=CC=C1.CN (C1=C (CNC2=C (C=NC (NC3=CC=C4NC (=O) CC4=C3) =N2) C (F) (F) F) C=CC=N1) S (C) (=O) =O |c:6,8,12,18,31,33,40,42, t:4,16,22,24|

C21H20F3N7O3S.C6H6O3S

665.66

Storage temperature: -20°C. Stability: ≥ 2 years