PF-00562271 (Synonyms: PF-562271;PF00562271;PF62271)

Cell lines

Squamous carcinoma cells

Preparation method

The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

1 μM, 48 hr

Applications

In squamous carcinoma cells, treatment of the FAK wt expressing cells with the FAK kinase inhibitor PF-562,271 resulted in a similar reduction in cell migration as seen in the FAK-/- cells. PF-562,271 dose-dependently inhibited FAK autophosphorylation on Y397. Treatment with PF-562,271 inhibited golgi orientation. PF-562,271 inhibited Pyk2 and Pyk2 autophosphorylation in PF-562,271 treated cells. Treatment of FAK wt cells with PF-562,271 dose-dependently inhibited cell proliferation. Treatment of FAK wt cells with PF-562,271 (0.25 μM) also resulted in a dose-dependent inhibition of colony formation. Treatment of cells with PF-562,271 in methylcellulose resulted in a small but significant reduction in the number of cells in S phase while the corresponding increase in G1 was not significant.

Animal models

Mice bearing PC-3M, BT474, BxPc3, and LoVo tumors,

Dosage form

Oral gavage, 25 to 50 mg/kg, twice daily

Application

In several human s.c. xenograft models, PF-562271 dose-dependently inhibited tumor growth, and produced maximum tumor inhibition for PC-3M, BT474, BxPc3, and LoVo ranging from 78% to 94% inhibition at doses of 25 to 50 mg/kg twice daily, without weight loss, morbidity, or death. PF-562271 (25 mg/kg by p.o.) significantly decreased tumor progression in both subcutaneous and bone metastasis PC3M-luc-C6 xenograft models.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Serrels A, McLeod K, Canel M, et al. The role of focal adhesion kinase catalytic activity on the proliferation and migration of squamous cell carcinoma cells[J]. International journal of cancer, 2012, 131(2): 287-297.

[2]. Roberts W G, Ung E, Whalen P, et al. Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271[J]. Cancer research, 2008, 68(6): 1935-1944.

[3]. Roberts W G, Ung E, Whalen P, et al. Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271[J]. Cancer research, 2008, 68(6): 1935-1944.