PF-573228

Names

[ Name ]:
PF-573228

[Synonym ]:
6-{[4-{[3-(Methylsulfonyl)benzyl]amino}-5-(trifluoromethyl)-2-pyrimidinyl]amino}-3,4-dihydro-2(1H)-quinolinone
6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one
6-{[4-{[3-(Methylsulfonyl)benzyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3,4-dihydroquinolin-2(1H)-one
cc-288
2(1H)-Quinolinone, 3,4-dihydro-6-[[4-[[[3-(methylsulfonyl)phenyl]methyl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]-
PF 573228
PF573228
PF-573228

Biological Activity

[Description]:

PF-573228 is a potent and selective FAK inhibitor with IC50 of 4 nM for purified recombinant catalytic fragment of FAK.

[Related Catalog]:

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FAK

Research Areas >> Cancer

[Target]

IC50: 4 nM (FAK)[1]

[In Vitro]

PF-573228 inhibits purified recombinant catalytic fragment of FAK with an IC50 of 4 nM. In cultured cells, PF-573228 inhibits FAK phosphorylation on Tyr397 with an IC50 of 30-100 nM. Treatment of cells with concentrations of PF-573228 that significantly decreased FAK Tyr397 phosphorylation fails to inhibit cell growth or induce apoptosis. In contrast, treatment with PF-573228 inhibits both chemotactic and haptotactic migration concomitant with the inhibition of focal adhesion turnover[1].

[Kinase Assay]

Purified activated FAK kinase domain is reacted with 50 μM ATP, and 10 μg/well of a random peptide polymer of Glu and Tyr (molar ratio of 4:1), poly (Glu/Tyr) in kinase buffer for 15 min. Phosphorylation of poly(Glu/Tyr) is challenged with s

[Cell Assay]

REF52 or PC3 cells are seeded into a 24-well plate in triplicate 24 h prior to daily treatment with the indicated concentrations of each inhibitor (PF-573228) for 3 days. Subsequently, the cells are harvested and counted. Apoptosis assays are performed using a cell death detection ELISA. REF52, PC3 or MDCKcells are treated for 24 h (16 h for MDCK) with the indicated concentrations of each inhibitor prior to lysis. Cells suspended for 16-24 h in serum-free medium served as a positive control. The cell lysates are incubated in duplicate in the ELISA system. The data represent the means±standard deviation of one of three experiments performed in duplicate[1].

[References]

[1]. Slack-Davis JK, et al. Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem. 2007 May 18;282(20):14845-52.

[Related Small Molecules]

Defactinib | PND-1186 | GSK2256098 | Benzol-1,2,4,5-tetramintetrahydrochlorid | PF-562271 | CEP-37440 | TAE226(NVP-TAE226) | PF-431396 | NAMI-A | Chloropyramine hydrochloride

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Molecular Formula ]:
C₂₂H₂₀F₃N₅O₃S

[ Molecular Weight ]:
491.486

[ Exact Mass ]:
491.123901

[ PSA ]:
121.46000

[ LogP ]:
1.03

[ Appearance of Characters ]:
white to off-white

[ Index of Refraction ]:
1.616

[ Storage condition ]:
Store at +4°C

[ Water Solubility ]:
DMSO: ≥20mg/mL

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301-H319

[ Precautionary Statements ]:
P301 + P310-P305 + P351 + P338

[ Hazard Codes ]:
T

[ Risk Phrases ]:
25-36

[ Safety Phrases ]:
26-45

[ RIDADR ]:
UN 2811 6.1 / PGIII

Articles

Integrin-specific control of focal adhesion kinase and RhoA regulates membrane protrusion and invasion.

PLoS ONE 8 , e74659, (2013)

Cell invasion through extracellular matrix (ECM) is a hallmark of the metastatic cascade. Cancer cells require adhesion to surrounding tissues for efficient migration to occur, which is mediated throu...