PF-00562271

Catalog No.S2672 Synonyms: PF-562271 Besylate

PF-00562271 Chemical Structure

Molecular Weight(MW): 665.66

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.

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  • Mol Ther 2012 20(5), 972-83. PF-00562271 purchased from Selleck.

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Biological Activity

Description 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.
Targets
FAK [1]
(Cell-free assay)
PYK2 [1]
(Cell-free assay)
CDK2/CyclinE [1]
(Cell-free assay)
CDK3/CyclinE [1]
(Cell-free assay)
CDK1/CyclinB [1]
(Cell-free assay)
1.5 nM 13 nM 30 nM 47 nM 58 nM
In vitro

PF-562271 shows the selective inhibitory effects on FAK and Pyk2 tyrosine kinase activity with IC50 of 1.5 nM and 14 nM, respectively. And in cell-based assays, the IC50 of PF-562271 is shown to be 5 nM for FAK, which is more selective compared to other kinase targets. [1] In 2 dimensional (2D) cultures, PF-562271 results in a dose-dependent cell proliferation inhibition in FAK WT, FAK−/− and FAK kinase-deficient (KD) cells with IC50 of 3.3 μM, 2.08 μM and 2.01 μM, respectively. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MV-4-11 cell NYLkUGlMT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MYPJcohq[mm2aX;uJI9nKGi3bXHuJG1XNTRvMUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlI4PjZizszN M2HsRnNCVkeHUh?=
human SW982 cell NFzBOHBIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NVvCNpd1UW6qaXLpeIlwdiCxZjDoeY1idiCVV{m4NkBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvOzJ6MjFOwG0> MVXTRW5ITVJ?
human KM12 cell Mmm5S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NXLGXlNuUW6qaXLpeIlwdiCxZjDoeY1idiCNTUGyJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{QDV3NzFOwG0> MWTTRW5ITVJ?
human COLO-205 cell M1r4Rmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M1PZRWlvcGmkaYTpc44hd2ZiaIXtZY4hS0:OTz2yNFUh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0xNjR6NkW4JO69VQ>? NWHlN3lbW0GQR1XS
human COLO-829 cell NH73VoVIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NGfWNGNKdmirYnn0bY9vKG:oIHj1cYFvKEORTF:tPFI6KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC55NkG3OkDPxE1? Ml7ZV2FPT0WU
human MG-63 cell NHTpNW1Iem:5dHigbY5pcWKrdHnvckBie3OjeR?= MVPJcohq[mm2aX;uJI9nKGi3bXHuJG1INTZ|IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MD64NFY{PyEQvF2= MkW5V2FPT0WU
human IGROV-1 cell MnrpS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NIH6[JpKdmirYnn0bY9vKG:oIHj1cYFvKEmJUl;WMVEh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0xNjhzMEO4JO69VQ>? M2Pjd3NCVkeHUh?=
human NCI-H650 cell M4jlRmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NIrV[ZRKdmirYnn0bY9vKG:oIHj1cYFvKE6FST3IOlUxKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC56M{G1OEDPxE1? NVezNW43W0GQR1XS
human RT-112 cell M17QNGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NUXmfmhDUW6qaXLpeIlwdiCxZjDoeY1idiCUVD2xNVIh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0xNjl6NE[g{txO MnLkV2FPT0WU
human BCPAP cell NIPQXVhIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M2P4VmlvcGmkaYTpc44hd2ZiaIXtZY4hSkOSQWCgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlAyOjh6IN88US=> MlPaV2FPT0WU
ALL-PO cell MYHHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MWfJcohq[mm2aX;uJI9nKGi3bXHuJGFNVC2STzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGuNFE2QDRizszN NELWPXNUSU6JRWK=
human KYSE-270 cell M2XMeGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M1n3VmlvcGmkaYTpc44hd2ZiaIXtZY4hU1mVRT2yO|Ah[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yNjB2N{G0JO69VQ>? NXfoNpR1W0GQR1XS
human 8305C cell NIDGUWJIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NWLTU|JkUW6qaXLpeIlwdiCxZjDoeY1idiB6M{C1R{Bk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvODl7MESg{txO MXjTRW5ITVJ?
NCI-H810 cell NGja[XFIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NID4S|lKdmirYnn0bY9vKG:oIHj1cYFvKE6FST3IPFExKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OS5zMEe3OkDPxE1? NX;pTJdkW0GQR1XS
human CAL-33 cell NF\4[IZIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M37BemlvcGmkaYTpc44hd2ZiaIXtZY4hS0GOLUOzJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4yOjl|ODFOwG0> MYPTRW5ITVJ?
human AN3-CA cell MUjHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MVLJcohq[mm2aX;uJI9nKGi3bXHuJGFPOy2FQTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGuNlE5PjdizszN MmXKV2FPT0WU
human NKM-1 cell NULjRploT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M33EeGlvcGmkaYTpc44hd2ZiaIXtZY4hVkuPLUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlI4PTB4IN88US=> NYnNTWIxW0GQR1XS
human BPH-1 cell MnXUS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NETYXm5KdmirYnn0bY9vKG:oIHj1cYFvKEKSSD2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4zQDd4NjFOwG0> MmToV2FPT0WU
human MES-SA cell NUTPcYJuT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NFWxOVVKdmirYnn0bY9vKG:oIHj1cYFvKE2HUz3TRUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvOzB4OEKg{txO MmK4V2FPT0WU
human CAL-62 cell M4fNXWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MYnJcohq[mm2aX;uJI9nKGi3bXHuJGNCVC14MjDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGuN|E6ODlizszN MoLmV2FPT0WU
human KYSE-150 cell NWTVSI5tT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NInYWGVKdmirYnn0bY9vKG:oIHj1cYFvKEu\U1WtNVUxKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OS5|NUKzOkDPxE1? M{LWeHNCVkeHUh?=
human SK-UT-1 cell MXXHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MnjKTY5pcWKrdHnvckBw\iCqdX3hckBUUy2XVD2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU41PDZ2NzFOwG0> MWfTRW5ITVJ?
human HUTU-80 cell Mm\kS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NWDsN|Z7UW6qaXLpeIlwdiCxZjDoeY1idiCKVWTVMVgxKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OS52NEi4OkDPxE1? Mn7vV2FPT0WU
human SIG-M5 cell NEHiSppIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NVr4NVUzUW6qaXLpeIlwdiCxZjDoeY1idiCVSVetUVUh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yNjR6NEi3JO69VQ>? M2Swd3NCVkeHUh?=
human AGS cell MlGwS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NXq0T2hCUW6qaXLpeIlwdiCxZjDoeY1idiCDR2OgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlUzOTJ2IN88US=> NFz5fINUSU6JRWK=
human ST486 cell M2nVdGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NFKzVoZKdmirYnn0bY9vKG:oIHj1cYFvKFOWNEi2JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU42OzJ5ODFOwG0> Ml3OV2FPT0WU
human HSC-2 cell NXTHUWV2T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MX7Jcohq[mm2aX;uJI9nKGi3bXHuJGhUSy1{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MT61N|k2KM7:TR?= MVnTRW5ITVJ?
human BC-1 cell MUPHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NGXLUXpKdmirYnn0bY9vKG:oIHj1cYFvKEKFLUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlYyPjZ2IN88US=> MV\TRW5ITVJ?
human CGTH-W-1 cell MkLFS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NYCxcXFpUW6qaXLpeIlwdiCxZjDoeY1idiCFR2TIMXcuOSClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTFwNkG2O|kh|ryP NUXJOoM4W0GQR1XS
human MZ1-PC cell NEPXV4VIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M3PjdGlvcGmkaYTpc44hd2ZiaIXtZY4hVVpzLWDDJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU43OjNzMjFOwG0> MWnTRW5ITVJ?
human SW1710 cell MkjCS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MVPJcohq[mm2aX;uJI9nKGi3bXHuJHNYOTdzMDDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGuOlI3OjhizszN NGqzeYNUSU6JRWK=
human EW-13 cell M3zUc2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NF3F[YFKdmirYnn0bY9vKG:oIHj1cYFvKEWZLUGzJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU43OzR4NjFOwG0> Mme5V2FPT0WU
human U251 cell NHnreIlIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NGn6[lJKdmirYnn0bY9vKG:oIHj1cYFvKFV{NUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlc1ODNzIN88US=> M365bnNCVkeHUh?=
human NCI-H460 cell NYC2SXlbT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NF;UXpVKdmirYnn0bY9vKG:oIHj1cYFvKE6FST3IOFYxKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:Oi5yNEizPUDPxE1? NWHK[oxpW0GQR1XS
human DU-4475 cell NHfRWI9Iem:5dHigbY5pcWKrdHnvckBie3OjeR?= NHfRc4dKdmirYnn0bY9vKG:oIHj1cYFvKESXLUS0O|Uh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0zNjF2N{W5JO69VQ>? MXjTRW5ITVJ?
human MFE-296 cell M2T3Rmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MoDkTY5pcWKrdHnvckBw\iCqdX3hckBOTkVvMkm2JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9Nk41Pzd7MjFOwG0> NYruN|RlW0GQR1XS
human DU-145 cell NIHvcnpIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NIHpNmNKdmirYnn0bY9vKG:oIHj1cYFvKESXLUG0OUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVIvPDlzMUig{txO MljlV2FPT0WU
human MDA-MB-231 cell NFjMWFRIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NWLBN|ZDUW6qaXLpeIlwdiCxZjDoeY1idiCPRFGtUWIuOjNzIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;Mj60PVU4OiEQvF2= MXzTRW5ITVJ?
human SNU-387 cell Mn3zS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MU\Jcohq[mm2aX;uJI9nKGi3bXHuJHNPXS1|OEegZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2yMlUzQDJizszN NXHUNIE1W0GQR1XS

... Click to View More Cell Line Experimental Data

In vivo In several human s.c. xenograft models, PF-562271 exhibits dose-dependent tumor growth inhibition, and produces 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. [1] PF-562271 (25 mg/kg by p.o.) leads to a significant decrease in tumor progression in both subcutaneous and bone metastasis PC3M-luc-C6 xenograft models. [3] In a Huh7.5 hepatocellular carcinoma xenograft model, combination therapy of sunitinib and PF-562271 targets angiogenesis and tumor aggressiveness, and produces more significant anti-tumor effect than single agent by blocking tumor growth and impacting the ability of the tumor to recover upon withdrawal of the therapy. [4]

Protocol

Kinase Assay:[1]
+ Expand

Recombinant kinase assay and enzyme kinetics :

Briefly, purified-activated FAK kinase domain (amino acid 410–689) is reacted with 50 μM ATP and 10 μg per well of a random peptide polymer of Glu and Tyr, p(Glu/Tyr), in kinase buffer [50 mM HEPES (pH 7.5), 125 mM NaCl, and 48 mM MgCl2] for 15 minutes. Phosphorylation of p(Glu/Tyr) is challenged with serially diluted PF-562271 at 1/2-Log concentrations starting at a top concentration of 1 μM. Each concentration is tested in triplicate. Phosphorylation of p(Glu/Tyr) is detected with a general antiphospho-tyrosine (PY20) antibody followed by horseradish peroxidase (HRP)-conjugated goat anti-mouse IgG antibody. HRP substrate is added, and absorbance readings at 450 nm are obtained after addition of stop solution (2 M H2SO4). IC50 values are determined using the Hill-Slope Model. Broad kinase selectivity profiling is performed in house and by using the KinaseProfiler Selectivity Screening Service available through UpState Biotechnology.
Cell Research:[2]
+ Expand
  • Cell lines: Squamous cell carcinoma (SCC)
  • Concentrations: 0 to 1 μM
  • Incubation Time: 72 hours
  • Method: Cells are plated for 48 hours before addition of PF-562271. After 3 days cells are fixed by addition of ice cold 25% trichloroacetic acid (TCA) solution prior to staining with Sulforhodamine B (SRB) dye solution. Plates are washed with 1% glacial acetic acid, air-dried and resuspended in 10 mM Tris buffer, pH 10.5 before reading absorbance at 540 nm. Curve fitting and generation of IC50 values is carried out using GraphPad Prism 4 software from six replicates.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: PC-3M, BT474, BxPc3, LoVo, U87MG, H125 and H460 cells are injected s.c. into the right flank of athymic female mice .
  • Formulation: PF-562271 is dissolved in 5% Gelucire.
  • Dosages: ≤100 mg/kg
  • Administration: Administered via p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 14 mg/mL warmed (21.03 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents individually and in order:
4% DMSO+30% PEG 300+ddH2O
3mg/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 665.66
Formula

C21H20F3N7O3S.C6H6O3S

CAS No. 939791-38-5
Storage powder
Synonyms PF-562271 Besylate

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00666926 Completed Head and Neck Neoplasm|Prostatic Neoplasm|Pancreatic Neoplasm Verastem, Inc. December 2005 Phase 1

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

If you have any other enquiries, please leave a message.

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Frequently Asked Questions

  • Question 1:

    What’s the difference between S2890 and S2672?

  • Answer:

    S2890 is free base and S2672 is the besylate salt, S2672 has better solubility than S2890.

  • Question 2:

    We are planning both in vitro and in vivo experiments and want to know how to reconstitute the drug for these purposes?

  • Answer:

    PF-00562271 has poor solubility in DMSO and water. Its solubility in DMSO is only 0.4mg/ml. In a previous literature report (http://www.ncbi.nlm.nih.gov/pubmed/18339875), the author used 5% Gelucire to formulate the compound. You can also consider other co-solvents such as PEG400, CMC, Tween80, and Captisol.

  • Question 3:

    Can you provide with a few common vehicles for PF-00562271, S2672 for use as oral gavage?

  • Answer:

    S2672 PF-00562271 can be dissolved in 0.5% CMC Na at 30 mg/ml as a suspension. If 4% DMSO can be used in your experiment, it will help dissolving the suspension more homogeneously.

FAK Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID