PF-573228

Catalog No.S2013

PF-573228 Chemical Structure

Molecular Weight(MW): 491.49

PF-573228 is an ATP-competitive inhibitor of FAK with IC50 of 4 nM in a cell-free assay, ~50- to 250-fold selective for FAK than Pyk2, CDK1/7 and GSK-3β.

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In DMSO USD 190 In stock
USD 147 In stock
USD 570 In stock
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Cited by 16 Publications

6 Customer Reviews

  • FAK inhibition blunted the increased migration induced by PGC1α depletion. G361 cells were subjected to 24 h transwell migration assays in the presence of DMSO or various doses of FAK inhibitor PF-573228. Images represent three pictures captured with scale bar representing 100 μm.

    Nature, 2016, 537(7620):422-429.. PF-573228 purchased from Selleck.

  • OVISE cells were incubated for 25 hr at the indicated concentrations of the FAK inhibitors. Immunoblots were performed to assess inhibition of auto-phosphorylation by the FAK inhibitors.

    PLoS One 2014 9(2), e88588. PF-573228 purchased from Selleck.

  • Cell growth inhibition of non-small cell lung carcinoma (NSCLC) by Focal adhesion kinase (FAK) inhibitor PF-573228. PF-573228 was applied on NCI-H460 and COR-L23, both derived from large cell lung carcinoma. Hence, it acted similarly showing strong inhibitory potential in both cell lines by suppressing the growth of 50% of cells between 4 and 7 礛.

    2014 Dr.Milica Pesic from Institute for Biological Research. PF-573228 purchased from Selleck.

  • (b) Using PF-573228 at a concentration range of 0.01–10 μM for 24 hours decreased phosphorylated FAK expression in a time-dependent manner, and there was a 70% inhibition rate at the range of 5–10 μM.

    Sci Rep, 2017, 7:43146. PF-573228 purchased from Selleck.

  • Effect of PF-228 (namely PF-573228) on EC actin stress fiber formation and FAK localization after thrombin. Confluent human pulmonary artery EC were pretreated with PF-228 (10 μM, 30 min) or vehicle and then stimulated with thrombin (1 U/ml, 5 min) or vehicle. (A) Immunofluorescent imaging of cells stained for F-actin (red) and FAK (green) was performed and representative images are shown. Increased actin stress fiber formation after thrombin with co-localization of FAK at the ends of stress fibers are noted (small and large arrows, respectively). (B) Quantification of actin stress fibers was performed separately and is expressed as a percentage of the total area imaged. (n=3 representative images from separate experiments for each experimental condition, *p < .05 compared to each other condition). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

    Vascul Pharmacol, 2018, doi:10.1016/j.vph.2018.06.017. PF-573228 purchased from Selleck.

  • a. Gelatin degradation by NCI-H460/R and COR-L23 cells treated with DOX, PF-573228, WZ811 and their combinations for 24 h. Images were captured using a 20× objective on a fluorescence microscope and representative examples are presented on the left part of the panel. At least 100 cells were analyzed per experiment. All experiments were performed at least three times. Merged channels show fluorescent gelatin (green), actin (red) and nuclei (blue) staining; dark areas represent spots of degraded gelatin. Scale bar = 100 μm. Corresponding histograms for each cell line are presented in the right part of the panel showing percentages of degraded gelatin areas relative to the cell volume. Each bar represents mean value ± S.E. * indicates p < 0.05 compared to untreated control cells; # indicates p < 0.05 compared to cells treated with PF-573228; $ indicates p < 0.05 compared to cells treated with WZ811.

    Cell Oncol (Dordr), 2017, 40(1):47-62.. PF-573228 purchased from Selleck.

Purity & Quality Control

Choose Selective FAK Inhibitors

Biological Activity

Description PF-573228 is an ATP-competitive inhibitor of FAK with IC50 of 4 nM in a cell-free assay, ~50- to 250-fold selective for FAK than Pyk2, CDK1/7 and GSK-3β.
Targets
FAK [1]
(Cell-free assay)
4 nM
In vitro

PF 573228 blocks the phosphorylation of FAK Tyr397 in REF52 cells, PC3 cells, SKOV-3 cells, L3.6p1 and F-G, MDCK cells with IC50 of 30-500 nM. However, PF 573228 (1 μM) with 80% inhibition of FAK phosphorylation fails to inhibit cell growth or apoptosis. Similar treatment of cells with PF-228 resulted in inhibition of serum or FN-directed migration and decreased focal adhesion turnover. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A431 MUXLbY5ie2ViYYPzZZk> M1\0Up4yOCEQvF2= Mn7OSG1UVw>? NGDIU4hqdmirYnn0d{BHSUticHjvd5Bpd3K7bHH0bY9vKHerdHigTWM2OCCxZjCxNUBvVQ>? MYSxO|M6PTV7NB?=
REF52 NFvHbGhMcW6jc3WgZZN{[Xl? Mk\VglExKM7:TR?= NXTib|dDTE2VTx?= NHriWo5qdmirYnn0d{B1cGVicHjvd5Bpd3K7bHH0bY9vKG:oIF\BT{BVgXJ|OUege4l1cCCLQ{WwJI9nKH5zMECgcm0> MYqxO|M6PTV7NB?=
PC3 NX;4dHR{U2mwYYPlJIF{e2G7 M3GzWJ4yOCEQvF2= MoXBSG1UVw>? NXHGO|NVcW6qaXLpeJMhfGinIIDoc5NxcG:{eXzheIlwdiCxZjDGRWshXHm{M{m3JJdqfGhiSVO1NEBw\iBzMECgcm0> NGXkencyPzN7NUW5OC=>
SKOV-3 MkLsT4lv[XOnIHHzd4F6 MnP2glExKM7:TR?= M4[zTGROW09? MY\pcohq[mm2czD0bIUheGixc4Doc5J6dGG2aX;uJI9nKE[DSzDUfZI{QTdid3n0bEBKSzVyIH;mJFUxKG6P NFruSHQyPzN7NUW5OC=>
L3.6p1 M4e5VWtqdmG|ZTDhd5NigQ>? NY\6d49ChjFyIN88US=> NWfWfolSTE2VTx?= NXfYUoxNcW6qaXLpeJMhfGinIIDoc5NxcG:{eXzheIlwdiCxZjDGRWshXHm{M{m3JJdqfGhiSVO1NEBw\iB|MECgcm0> MVixO|M6PTV7NB?=
F-G M3z2TGtqdmG|ZTDhd5NigQ>? MUL+NVAh|ryP NIPkfmFFVVOR NUjRV|FKcW6qaXLpeJMhfGinIIDoc5NxcG:{eXzheIlwdiCxZjDGRWshXHm{M{m3JJdqfGhiSVO1NEBw\iB|MDDuUS=> NXW0XVk{OTd|OUW1PVQ>
MDCK NIrwPYxMcW6jc3WgZZN{[Xl? NUG2eZhohjFyIN88US=> NE[5TnBFVVOR MYTpcohq[mm2czD0bIUheGixc4Doc5J6dGG2aX;uJI9nKE[DSzDUfZI{QTdid3n0bEBKSzVyIH;mJFUxOCCwTR?= NIrjNlIyPzN7NUW5OC=>
PC3 MonxS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MYmxNEDPxE1? NFjOTZJFVVOR NEX3SFh{cWewaX\pZ4FvfGy7IHnubIljcXS|IHPlcIwh\3Kxd4ToMi=> MYqxO|M6PTV7NB?=
REF52 NUT5emU1T3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NV;IZ4I1OTBizszN MV\EUXNQ MUjzbYdvcW[rY3HueIx6KGmwaHnibZR{KGOnbHyg[5Jwf3SqLh?= M17iXlE4Ozl3NUm0
MDCK MonBRZBweHSxc3nzJIF{e2G7 NF;iRlAyOCEQvF2= MYTEUXNQ NYS5[3ZRcW6mdXPld{BieG:ydH;zbZM> NYnxVJFMOTd|OUW1PVQ>
REF52 MVTBdI9xfG:|aYOgZZN{[Xl? MlvPNVAh|ryP NH7HXWZFVVOR NVKwNYY1cW6mdXPld{BieG:ydH;zbZM> NI\UemkyPzN7NUW5OC=>
REF52 NImzdHdHfW6ldHnvckBie3OjeR?= NFnGNYsyOCEQvF2= NHvOWXNFVVOR MV3icI9kc3Nic3XyeY0h[W6mIF\OMZN1cW23bHH0[YQhdWmpcnH0bY9v M1my[|E4Ozl3NUm0
platelet MlK5SpVv[3Srb36gZZN{[Xl? NXmzR2I6OSEQvF2= M3jzSmROW09? M{TkbYlvcGmkaYTzJJBt[XSnbHX0JIFo\3KnZ3H0bY9vKGGwZDDzdJJm[WSrbne= M{HySFE6PzF4OECz
platelet MnHHSpVv[3Srb36gZZN{[Xl? NV\xTJR[OSEQvF2= M4DyTmROW09? M3qwSoxm[WS|IITvJIlvcGmkaYTpc44hd2ZiUFHLJIFv\CCDS2S= MVqxPVcyPjhyMx?=
platelet NYf5WZdETnWwY4Tpc44h[XO|YYm= MXyxJO69VQ>? NVH1N3VlTE2VTx?= NFzUN5RjdG:la4OgZ4Ft[2m3bTDtc4JqdGm8YYTpc44h[W6mIHTlcpNmKGe{YX71cIUhe2WlcnX0bY9v MkfPNVk4OTZ6MEO=
4T1 MWXGeY5kfGmxbjDhd5NigQ>? MoWySG1UVw>? M{\XUIFjd2yrc3jld{B1cGViaX70[ZJi[3Srb36gZoV1f2WnbjFOtlMhcW62ZXfybY4h[W6mIGVOtnIuUUl? MX:xPVc1ODR|Mx?=
MCF7 M1z4O2tqdmG|ZTDhd5NigQ>? M{C2Sp4yOCEQvF2= MVnEUXNQ M3fEcYlvcGmkaYTzJJRp\SCyaH;zdIhwenmuYYTpc44hd2ZiRlHLJHR6ejN7NzD3bZRpKEmFNUCgc4YhPDNyIH7N NETrWnUzODN3NEe4NC=>
TamR MlixT4lv[XOnIHHzd4F6 MWH+NVAh|ryP NGLiVYVFVVOR MUDpcohq[mm2czD0bIUheGixc4Doc5J6dGG2aX;uJI9nKE[DSzDUfZI{QTdid3n0bEBKSzVyIH;mJFUxKG6P NGnsVWgzODN3NEe4NC=>
FasR NYPoT21OU2mwYYPlJIF{e2G7 MnjaglExKM7:TR?= M1PZPGROW09? NG\wZ4dqdmirYnn0d{B1cGVicHjvd5Bpd3K7bHH0bY9vKG:oIF\BT{BVgXJ|OUege4l1cCCLQ{WwJI9nKDF|MDDuUS=> NX7BbJdQOjB|NUS3PFA>
TamR NFvvNI1HfW6ldHnvckBie3OjeR?= MUixJO69VQ>? M4G1dmROW09? MmPRbY5pcWKrdIOgZ4VtdCCvaXfyZZRqd25? Ml7FNlA{PTR5OEC=
FasR NXn2eYN2TnWwY4Tpc44h[XO|YYm= MojKNUDPxE1? NUnDPYg3TE2VTx?= M{TX[YlvcGmkaYTzJINmdGxibXnndoF1cW:w M4HIbFIxOzV2N{iw
endothelial cell MYrLbY5ie2ViYYPzZZk> MlzHOFAhdk1? MnKySG1UVw>? M3v4fYlvcGmkaYTzJGgzVzJvaX7keYNm\CCyaH;zdIhwenmuYYTpc44hd2ZiRlHL NHTZd2EzOTJzMkSwNi=>
endothelial cell NFfZR|hHfW6ldHnvckBie3OjeR?= MkXIOFAhdk1? MlLnSG1UVw>? NIO2U2lqdmirYnn0d{BJOk9{LXnu[JVk\WRic4Ty[ZN{KG[rYnXyJIZwem2jdHnvci=> NYDKfpJxOjF{MUK0NFI>
endothelial cell NY\3OnExSXCxcITvd4l{KGG|c3H5 Mm\HOFAhdk1? MonXSG1UVw>? M1jEV4lvcGmkaYTzJIFxd3C2b4Ppdy=> MU[yNVIyOjRyMh?=
GH3 M{TRfWZ2dmO2aX;uJIF{e2G7 MlTtN{DPxE1? NXW1Z4ZmTE2VTx?= M2WzTIlv[3KnYYPld{BKUyiFYTmgZY1xdGm2dXTl MUGyNVkzPTVzMh?=
GH3 M2H5cmZ2dmO2aX;uJIF{e2G7 M13TblMh|ryP NEG5SVdFVVOR MoCz[Y5p[W6lZYOgRmtE[S2laHHucoVtKGGldHn2bZR6 NFXWbGUzOTl{NUWxNi=>
HUVEC MlHHZ5l1d3SxeHnjbZR6KGG|c3H5 MljRglExKM7:TR?= M3fPTWROW09? NYDaW3FScW2yYXnyd{BmdmSxdHjlcIlidCClZXzsJJZq[WKrbHn0fS=> MWOyNlA4PTB3Nx?=
HUVEC NUPCemNjU2mwYYPlJIF{e2G7 MkK3OUDPxE1? MV3EUXNQ M4PUcolvcGmkaYTzJGZCUyCtaX7hd4Uh[WO2aY\peJk> MonpNlIxPzVyNUe=
HUVEC NYi2c483TnWwY4Tpc44h[XO|YYm= MWi1JO69VQ>? NUj0WYF4TE2VTx?= MVfpcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2 NHTDe|kzOjB5NUC1Oy=>
HUVEC MYjBdI9xfG:|aYOgZZN{[Xl? NX3xZVc5PSEQvF2= NIH0e4NFVVOR NWfXfXhscW6mdXPld{BieG:ydH;zbZM> NFj0VmszOjB5NUC1Oy=>
HUVEC NWjT[IxoTnWwY4Tpc44h[XO|YYm= M{e1Z|Uh|ryP NXPocZdSTE2VTx?= NYjhcHoxcW2yZXTld{BmdmSxdHjlcIlidCClZXzsJI1q\3KjdHnvckBidmRiYXz0[ZJ{KHSqZTDj[YxtfWyjcjDhZ5RqdiCleYTvd4tmdGW2b36= NGjKeVIzOjB5NUC1Oy=>
HUVEC MYXGeY5kfGmxbjDhd5NigQ>? NX;mUYk5PSEQvF2= MYnEUXNQ M37SdYJtd2OtczDIWXZGSyC|cILveZRqdmdib36gZ49tdGGpZX6gTUBo\Wy| NF7GSGczOjB5NUC1Oy=>
human peripheral blood T cells NWfWbZhLU2mwYYPlJIF{e2G7 NETUR2x,OTBizszN NUfuZZhbTE2VTx?= M1;Vb4lvcGmkaYTzJJNqfGVvc4DlZ4lncWNicHjvd5Bpd3K7bHH0bY9vKG:oIF\BTy=> M4\3R|I{QTJ6MUi4
human peripheral blood T cells M3PMeGZ2dmO2aX;uJIF{e2G7 MkfLglExKM7:TR?= MlfRSG1UVw>? M3y2OYlueGGrcoOgWGNTNWmwZIXj[YQhXCClZXzsJI1wenCqb3zv[4lk[WxiY3jhcodmeyCjbnSgZYx1\XK|IHHjeIl3cXS7IH;mJHJpd0F? MoHTNlM6OjhzOEi=
human peripheral blood T cells M4nESGZ2dmO2aX;uJIF{e2G7 MYj+NVAh|ryP NI[1NGpFVVOR NGryVnlqdmirYnn0d{BxcG:|cHjvdplt[XSrb36gc4YhYkGSLUewJIFv\CCOQWS= NFntSHozOzl{OEG4PC=>
human peripheral blood T cells M2X2Z2Z2dmO2aX;uJIF{e2G7 MV\+NVAh|ryP NFvoXJBFVVOR M1XpZ4lueGGrcoOgRY51cWenbj3k[ZBmdmSnboSgWEBk\WyuIHPvcop2\2G2aX;u NVLnUIZLOjN7MkixPFg>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
cyclin B1; 

PubMed: 30761269     


(D) On the third day, PF-573228-treated cells were harvested and subjected to Western blot analysis for cyclin B1. Cyclin B1 levels were much higher in A549 cells with 1 μM PF-573228 or without PF-573228 treatment than in the cells treated with higher concentrations of PF-573228. (E) After 10 μM PF-573228 treatment, cyclin B1 levels declined markedly in H460 cells. (F) PF-573228 administration slightly reduced cyclin B1 levels in H1299 cells. 

p-FAK / FAK ; 

PubMed: 30761269     


FAK expression levels and FAK activity, as measured by the phosphorylation of FAK at tyrosine 576 and 577, were quantified by Western blot analysis after treatment of lung cancer cells with PF-573228 for 3 days.

Lamin A / Lamin C; 

PubMed: 30761269     


(B) The cells treated with 10 μM PF-573228 exhibited a decrease in p-FAK levels. Lamin A and lamin C expression levels were much lower in A549 cells exposed to 10 μM PF-573228. 

30761269
Immunofluorescence
FAK / F-actin; 

PubMed: 30761269     


(B) The cells were stained with phalloidin to visualize F-actin (red) and a FAK antibody to visualize the FAK distribution (green). In cells without PF-573228 administration, FAK translocated to focal adhesions at the tips of actin stress fibers, and the focal adhesions were relatively large. When cells were exposed to 10 μM PF-573228, FAK translocation to focal adhesions was reduced, and the sizes of the focal adhesions were smaller. Nuclei in cells treated with PF-573228 were deformed, as visualized with DAPI staining, whereas most nuclei in cells without PF-573228 treatment were oval shaped. 

Emerin; 

PubMed: 30761269     


(A) After PF-573228 treatment of A549 cells, the cells were fixed and stained with phalloidin to label F-actin (red) and an antibody against emerin (green) to outline the nuclear shape. Cells treated with PF-573228 were extremely large and had deformed nuclei, whereas mostly oval-like nuclei were present in the cells without PF-573228 treatment. 

30761269
Growth inhibition assay
Cell viability; 

PubMed: 30761269     


Three different types of lung cancer cells, (A) A549 lung adenocarcinoma and (B) H460, and (C) H1299 large cell carcinoma, were selected for the PF-573228 administration regimen. Cell growth curves of the three lung cancer cell lines treated with various doses of PF-573228 for 4 days were established. The administration of PF-573228 at 10 μM to the lung cancer cells effectively suppressed cell growth in vitro, as proliferative activity totally ceased in the cells exposed to 10 μM PF-573228.

30761269
In vivo Inhibition of FAK by PF-573,228 in Ctrl-MT mice leads to a significant suppression of mammary tumorigenesis as well as lung metastasis. In contrast, treatment of MFCKO-MT mice with PF-573,228 did not affect the initiation of mammary tumors in these mice, as would be expected due to the absence of FAK in mammary epithelial cells of these mice [2].

Protocol

Kinase Assay:

[1]

+ Expand

Affinity determination:

Purified activated FAK kinase domain (amino acids 410–689) 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 (50 mM HEPES, pH 7.5, 125 mM NaCl, 48 mM MgCl2) for 15 min. Phosphorylation of poly(Glu/Tyr) is challenged with serially diluted compounds at 1/2-Log concentrations starting at a top concentration of 1 μM. Each concentration is run in triplicate. Phosphorylation of poly(Glu/Tyr) is detected with a general anti-phospho-tyrosine (PY20) antibody, followed by horseradish peroxidase-conjugated goat anti-mouse IgG antibody. The standard horseradish peroxidase substrate 3, 3
Cell Research:

[1]

+ Expand
  • Cell lines: REF52 or PC3 cells
  • Concentrations: ~10 μM
  • Incubation Time: 3 days
  • Method:

    Growth assays are performed by seeding 1 × 104 REF52 or PC3 cells/well of a 24-well plate in triplicate 24 h prior to daily treatment with the indicated concentrations of each inhibitor for 3 days. Subsequently, the cells are harvested and counted.


    (Only for Reference)
Animal Research:

[2]

+ Expand
  • Animal Models: Ctrl-MT and MFCKO-MT mice
  • Formulation: --
  • Dosages: 5 mg/kg
  • Administration: oral administration
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 26 mg/mL (52.9 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5% DMSO+2% Tween 80+30% PEG 300+ddH2O
For best results, use promptly after mixing.
5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 491.49
Formula

C22H20F3N5O3S

CAS No. 869288-64-2
Storage powder
in solvent
Synonyms N/A

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Frequently Asked Questions

  • Question 1:

    Would you please let me know the detail of how to dissolve PF-573228 (Catalog No.S2013) for in vivo study (oral administration)?

  • Answer:

    PF-573228 in 30% PEG400+0.5% Tween80+ 5% Propylene glycol at 30mg/ml is a suspension. If you will use the compound for oral gavage, this suspension is fine for it.

FAK Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID