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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Choose Selective FAK Inhibitors

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 NUjEdFZmT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NYDMdmZXUW6qaXLpeIlwdiCxZjDoeY1idiCPVj20MVEyKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC5{N{[2JO69VQ>? NUX0PWxjW0GQR1XS
human SW982 cell NXnFNZhQT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NF\ZR4pKdmirYnn0bY9vKG:oIHj1cYFvKFOZOUiyJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{Ojh{IN88US=> M3nJd3NCVkeHUh?=
human KM12 cell MYPHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NX\GeVJmUW6qaXLpeIlwdiCxZjDoeY1idiCNTUGyJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{QDV3NzFOwG0> NYLrS25vW0GQR1XS
human COLO-205 cell NUXW[mFOT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MXXJcohq[mm2aX;uJI9nKGi3bXHuJGNQVE9vMkC1JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE41QDZ3ODFOwG0> MmfrV2FPT0WU
human COLO-829 cell MlvHS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NUfHU5NIUW6qaXLpeIlwdiCxZjDoeY1idiCFT1zPMVgzQSClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTBwN{[xO|Yh|ryP MUDTRW5ITVJ?
human MG-63 cell NFP3WWhIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M3q2WGlvcGmkaYTpc44hd2ZiaIXtZY4hVUdvNkOgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlgxPjN5IN88US=> M1KxSXNCVkeHUh?=
human IGROV-1 cell MoTlS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MWfJcohq[mm2aX;uJI9nKGi3bXHuJGlIWk:YLUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlgyODN6IN88US=> NWTjb21LW0GQR1XS
human NCI-H650 cell NFfsOpJIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NIrGcm5KdmirYnn0bY9vKG:oIHj1cYFvKE6FST3IOlUxKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC56M{G1OEDPxE1? Mn\VV2FPT0WU
human RT-112 cell MmOwS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NGDFN|BKdmirYnn0bY9vKG:oIHj1cYFvKFKWLUGxNkBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvQTh2NjFOwG0> NXH0VGF[W0GQR1XS
human BCPAP cell MX7Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NIK1bnZKdmirYnn0bY9vKG:oIHj1cYFvKEKFUFHQJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4xOTJ6ODFOwG0> M1fidnNCVkeHUh?=
ALL-PO cell Mo\hS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M3n6cGlvcGmkaYTpc44hd2ZiaIXtZY4hSUyOLWDPJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4xOTV6NDFOwG0> NXj1UVRDW0GQR1XS
human KYSE-270 cell NF6w[4VIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MVPJcohq[mm2aX;uJI9nKGi3bXHuJGt[W0VvMkewJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4xPDdzNDFOwG0> M1:1e3NCVkeHUh?=
human 8305C cell Mof2S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M{X3VmlvcGmkaYTpc44hd2ZiaIXtZY4hQDNyNVOgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlA6QTB2IN88US=> M2PONHNCVkeHUh?=
NCI-H810 cell MWTHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MX\Jcohq[mm2aX;uJI9nKGi3bXHuJG5EUS2KOEGwJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4yODd5NjFOwG0> MV7TRW5ITVJ?
human CAL-33 cell MlTaS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MXrJcohq[mm2aX;uJI9nKGi3bXHuJGNCVC1|MzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGuNVI6OzhizszN NVTXcolxW0GQR1XS
human AN3-CA cell MmSwS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MXnJcohq[mm2aX;uJI9nKGi3bXHuJGFPOy2FQTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGuNlE5PjdizszN NGnFUHBUSU6JRWK=
human NKM-1 cell MkC0S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NVraNYdHUW6qaXLpeIlwdiCxZjDoeY1idiCQS12tNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvOjd3ME[g{txO NGTRSpdUSU6JRWK=
human BPH-1 cell NX3WZWNVT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NFG3bXZKdmirYnn0bY9vKG:oIHj1cYFvKEKSSD2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4zQDd4NjFOwG0> NWHVR|dQW0GQR1XS
human MES-SA cell M1n0Tmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NYDybWprUW6qaXLpeIlwdiCxZjDoeY1idiCPRWOtV2Eh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yNjNyNkiyJO69VQ>? M4jU[nNCVkeHUh?=
human CAL-62 cell MXPHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M1T0R2lvcGmkaYTpc44hd2ZiaIXtZY4hS0GOLU[yJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4{OTlyOTFOwG0> NUDxdW5uW0GQR1XS
human KYSE-150 cell MXvHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M1SwbGlvcGmkaYTpc44hd2ZiaIXtZY4hU1mVRT2xOVAh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yNjN3MkO2JO69VQ>? NX[0OpBYW0GQR1XS
human SK-UT-1 cell NGK2NWtIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MmjsTY5pcWKrdHnvckBw\iCqdX3hckBUUy2XVD2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU41PDZ2NzFOwG0> NEfIZVZUSU6JRWK=
human HUTU-80 cell M4PSW2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NFnBdlVKdmirYnn0bY9vKG:oIHj1cYFvKEiXVGWtPFAh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yNjR2OEi2JO69VQ>? M3PQWHNCVkeHUh?=
human SIG-M5 cell Mo\VS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NHfyb5JKdmirYnn0bY9vKG:oIHj1cYFvKFOLRz3NOUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvPDh2OEeg{txO NFvnOIRUSU6JRWK=
human AGS cell M3nKNGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MlTUTY5pcWKrdHnvckBw\iCqdX3hckBCT1NiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1zLkWyNVI1KM7:TR?= MUfTRW5ITVJ?
human ST486 cell M4njW2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NEfLWI5KdmirYnn0bY9vKG:oIHj1cYFvKFOWNEi2JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU42OzJ5ODFOwG0> NVLON5NLW0GQR1XS
human HSC-2 cell NW\mToJyT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MVrJcohq[mm2aX;uJI9nKGi3bXHuJGhUSy1{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MT61N|k2KM7:TR?= MUnTRW5ITVJ?
human BC-1 cell NFXUfGpIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MoL2TY5pcWKrdHnvckBw\iCqdX3hckBDSy1zIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MT62NVY3PCEQvF2= M2TzeXNCVkeHUh?=
human CGTH-W-1 cell NUDCR25zT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= Mo\xTY5pcWKrdHnvckBw\iCqdX3hckBET1SKLWetNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvPjF4N{mg{txO M2LyWXNCVkeHUh?=
human MZ1-PC cell MmHMS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NHT5c4lKdmirYnn0bY9vKG:oIHj1cYFvKE2cMT3QR{Bk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvPjJ|MUKg{txO MkO2V2FPT0WU
human SW1710 cell NFHWN4lIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NITmUlNKdmirYnn0bY9vKG:oIHj1cYFvKFOZMUexNEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvPjJ4Mkig{txO M1zYNHNCVkeHUh?=
human EW-13 cell NF30cJdIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NGfCT4xKdmirYnn0bY9vKG:oIHj1cYFvKEWZLUGzJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU43OzR4NjFOwG0> NWmzVm5{W0GQR1XS
human U251 cell NVXqe3EyT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NVfZblhwUW6qaXLpeIlwdiCxZjDoeY1idiCXMkWxJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU44PDB|MTFOwG0> MUjTRW5ITVJ?
human NCI-H460 cell NX\x[2Q2T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NHz1[VBKdmirYnn0bY9vKG:oIHj1cYFvKE6FST3IOFYxKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:Oi5yNEizPUDPxE1? MX3TRW5ITVJ?
human DU-4475 cell MVHHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NXLSN5JCUW6qaXLpeIlwdiCxZjDoeY1idiCGVT20OFc2KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:Oi5zNEe1PUDPxE1? M3\VW3NCVkeHUh?=
human MFE-296 cell NWL5NYlqT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MX;Jcohq[mm2aX;uJI9nKGi3bXHuJG1HTS1{OU[gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2yMlQ4Pzl{IN88US=> NX31SoxmW0GQR1XS
human DU-145 cell NIDlflJIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MUfJcohq[mm2aX;uJI9nKGi3bXHuJGRWNTF2NTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUKuOFkyOThizszN MoX1V2FPT0WU
human MDA-MB-231 cell MYrHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NX\TV5FoUW6qaXLpeIlwdiCxZjDoeY1idiCPRFGtUWIuOjNzIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;Mj60PVU4OiEQvF2= NYnCdo9lW0GQR1XS
human SNU-387 cell MYTHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NITvb5pKdmirYnn0bY9vKG:oIHj1cYFvKFOQVT2zPFch[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0zNjV{OEKg{txO NXnWPI9KW0GQR1XS

... 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 to the product individually and in order:
4% DMSO+30% PEG 300+ddH2O
For best results, use promptly after mixing.
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:

    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 2:

    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