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 NHTIdGFIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M33WPGlvcGmkaYTpc44hd2ZiaIXtZY4hVVZvND2xNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvOjd4NjFOwG0> M2\FPHNCVkeHUh?=
human SW982 cell MX3Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MXjJcohq[mm2aX;uJI9nKGi3bXHuJHNYQTh{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MD6zNlgzKM7:TR?= NYLxfpd6W0GQR1XS
human KM12 cell MoXZS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NEfiT2VKdmirYnn0bY9vKG:oIHj1cYFvKEuPMUKgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlM5PTV5IN88US=> MVHTRW5ITVJ?
human COLO-205 cell NHrXW49Iem:5dHigbY5pcWKrdHnvckBie3OjeR?= MYXJcohq[mm2aX;uJI9nKGi3bXHuJGNQVE9vMkC1JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE41QDZ3ODFOwG0> NInxTVZUSU6JRWK=
human COLO-829 cell NV\2XFlrT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= Mk\5TY5pcWKrdHnvckBw\iCqdX3hckBEV0yRLUiyPUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvPzZzN{[g{txO NFrZdYJUSU6JRWK=
human MG-63 cell MVXHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M2\0R2lvcGmkaYTpc44hd2ZiaIXtZY4hVUdvNkOgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2wMlgxPjN5IN88US=> MlPQV2FPT0WU
human IGROV-1 cell M1vkSWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M4\mVmlvcGmkaYTpc44hd2ZiaIXtZY4hUUeUT2[tNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvQDFyM{ig{txO M4\RPXNCVkeHUh?=
human NCI-H650 cell MVPHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MnrmTY5pcWKrdHnvckBw\iCqdX3hckBPS0lvSE[1NEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvQDNzNUSg{txO MYnTRW5ITVJ?
human RT-112 cell M2X0XWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NHPnU2dKdmirYnn0bY9vKG:oIHj1cYFvKFKWLUGxNkBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvQTh2NjFOwG0> M{nCOHNCVkeHUh?=
human BCPAP cell M1\yOWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MUTJcohq[mm2aX;uJI9nKGi3bXHuJGJEWEGSIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MT6wNVI5QCEQvF2= NHLUZYVUSU6JRWK=
ALL-PO cell M3rpb2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 Mn7LTY5pcWKrdHnvckBw\iCqdX3hckBCVExvUF:gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlAyPTh2IN88US=> NUf4PFlyW0GQR1XS
human KYSE-270 cell MV;Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MVjJcohq[mm2aX;uJI9nKGi3bXHuJGt[W0VvMkewJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4xPDdzNDFOwG0> M{TBOXNCVkeHUh?=
human 8305C cell NEP1PXpIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MoD2TY5pcWKrdHnvckBw\iCqdX3hckA5OzB3QzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGuNFk6ODRizszN Mk\6V2FPT0WU
NCI-H810 cell NF76WmtIem:5dHigbY5pcWKrdHnvckBie3OjeR?= Mke2TY5pcWKrdHnvckBw\iCqdX3hckBPS0lvSEixNEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvOTB5N{[g{txO M2SxeHNCVkeHUh?=
human CAL-33 cell NGL0PIFIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MYfJcohq[mm2aX;uJI9nKGi3bXHuJGNCVC1|MzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGuNVI6OzhizszN MmHtV2FPT0WU
human AN3-CA cell NETNT|dIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MXPJcohq[mm2aX;uJI9nKGi3bXHuJGFPOy2FQTDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGuNlE5PjdizszN NUTGOGlUW0GQR1XS
human NKM-1 cell NXzJdIdjT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NX3rNXE2UW6qaXLpeIlwdiCxZjDoeY1idiCQS12tNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvOjd3ME[g{txO NUm3OVVFW0GQR1XS
human BPH-1 cell MXHHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NEnMZ2VKdmirYnn0bY9vKG:oIHj1cYFvKEKSSD2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4zQDd4NjFOwG0> MXvTRW5ITVJ?
human MES-SA cell NWH4R3NYT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M3LmUWlvcGmkaYTpc44hd2ZiaIXtZY4hVUWVLWPBJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4{ODZ6MjFOwG0> MX7TRW5ITVJ?
human CAL-62 cell M{TqRmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M4HFTmlvcGmkaYTpc44hd2ZiaIXtZY4hS0GOLU[yJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4{OTlyOTFOwG0> M1u4[3NCVkeHUh?=
human KYSE-150 cell MUDHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MXjJcohq[mm2aX;uJI9nKGi3bXHuJGt[W0VvMUWwJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4{PTJ|NjFOwG0> MX;TRW5ITVJ?
human SK-UT-1 cell MYnHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NYiwZmN1UW6qaXLpeIlwdiCxZjDoeY1idiCVSz3VWE0yKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OS52NE[0O{DPxE1? NFy2[mVUSU6JRWK=
human HUTU-80 cell NYXkWGdOT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MlrBTY5pcWKrdHnvckBw\iCqdX3hckBJXVSXLUiwJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU41PDh6NjFOwG0> NIrJcnRUSU6JRWK=
human SIG-M5 cell NYe3SIRIT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NFLhd4FKdmirYnn0bY9vKG:oIHj1cYFvKFOLRz3NOUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvPDh2OEeg{txO MmDBV2FPT0WU
human AGS cell NXT0VJlCT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= Mk\5TY5pcWKrdHnvckBw\iCqdX3hckBCT1NiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1zLkWyNVI1KM7:TR?= MUDTRW5ITVJ?
human ST486 cell MnnwS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NFjYOJlKdmirYnn0bY9vKG:oIHj1cYFvKFOWNEi2JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU42OzJ5ODFOwG0> MoDsV2FPT0WU
human HSC-2 cell NVLVcFkyT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MnPLTY5pcWKrdHnvckBw\iCqdX3hckBJW0NvMjDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGuOVM6PSEQvF2= MXjTRW5ITVJ?
human BC-1 cell NGraSlhIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NIfPZlRKdmirYnn0bY9vKG:oIHj1cYFvKEKFLUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlYyPjZ2IN88US=> MXXTRW5ITVJ?
human CGTH-W-1 cell NG\uUm9Iem:5dHigbY5pcWKrdHnvckBie3OjeR?= MUnJcohq[mm2aX;uJI9nKGi3bXHuJGNIXEhvVz2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU43OTZ5OTFOwG0> MXLTRW5ITVJ?
human MZ1-PC cell MUHHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M4PkfGlvcGmkaYTpc44hd2ZiaIXtZY4hVVpzLWDDJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU43OjNzMjFOwG0> M2rjWHNCVkeHUh?=
human SW1710 cell M{m5bGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NHvJfHBKdmirYnn0bY9vKG:oIHj1cYFvKFOZMUexNEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvPjJ4Mkig{txO MYXTRW5ITVJ?
human EW-13 cell NVXYd2dpT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= Mor3TY5pcWKrdHnvckBw\iCqdX3hckBGXy1zMzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGuOlM1PjZizszN NGGxNYNUSU6JRWK=
human U251 cell MYPHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MWHJcohq[mm2aX;uJI9nKGi3bXHuJHUzPTFiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1zLke0NFMyKM7:TR?= MUjTRW5ITVJ?
human NCI-H460 cell NILKPIRIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MnTxTY5pcWKrdHnvckBw\iCqdX3hckBPS0lvSES2NEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVIvODR6M{mg{txO NETCZlZUSU6JRWK=
human DU-4475 cell NV\XT5lTT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M3LUTGlvcGmkaYTpc44hd2ZiaIXtZY4hTFVvNES3OUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVIvOTR5NUmg{txO MVXTRW5ITVJ?
human MFE-296 cell NXW3VYFpT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= Mk\JTY5pcWKrdHnvckBw\iCqdX3hckBOTkVvMkm2JINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9Nk41Pzd7MjFOwG0> MkDEV2FPT0WU
human DU-145 cell Mn7BS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NYXwbVFNUW6qaXLpeIlwdiCxZjDoeY1idiCGVT2xOFUh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0zNjR7MUG4JO69VQ>? M3SyWXNCVkeHUh?=
human MDA-MB-231 cell MkTES5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NUDJ[Ix7UW6qaXLpeIlwdiCxZjDoeY1idiCPRFGtUWIuOjNzIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;Mj60PVU4OiEQvF2= M1fud3NCVkeHUh?=
human SNU-387 cell M{njPWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NEH3fGZKdmirYnn0bY9vKG:oIHj1cYFvKFOQVT2zPFch[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0zNjV{OEKg{txO MVTTRW5ITVJ?

... 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
in solvent
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