PF-00562271 Besylate

For research use only.

Catalog No.S2672 Synonyms: PF-562271 Besylate

9 publications

PF-00562271 Besylate Chemical Structure

CAS No. 939791-38-5

PF-00562271 Besylate (PF-562271) 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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Selleck's PF-00562271 Besylate has been cited by 9 publications

4 Customer Reviews

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

    Pharmacological inhibition of optoFAK with the ATP-competitive FAK inhibitor PF-00562271. OptoFAK expressing SC4 cells were serum-starved for 24 h in the absence or presence of PF-00562271 (1 mM) before being illuminated for 10 min with blue light (451 nm, 2 μmol m-2 s-1) or kept in the dark.

    Cell Signal, 2018, 42:176-183. PF-00562271 Besylate purchased from Selleck.

  • The migration index enhanced by CX3CL1 was dramatic reduced using Bosutinib and PF-00562271. CX3CL1-only group as control. Scale bar = 200 μm. The experiments were repeated three times. *P< 0.05, **P< 0.01, ***P< 0.001, ****P< 0.0001.

    J Cancer, 2018, 9(19):3603-3612. PF-00562271 Besylate purchased from Selleck.

    SGC-7901 and MGC-803 cells were treated with OLFM4-sh lentivirus or FAK inhibitor (PF) alone, or co-treated with OLFM4-sh lentivirus and PF. Cellular invasive ability was measured by transwell assay after indicated treatment. Data are expressed as mean ± standard deviation from three independent experiments. One was analysis of variance (ANOVA) with Bonferroni T post-test was used to analysis the data. *P < 0.05, ***P < 0.001; ##P < 0.01, ###P < 0.001 VS. OLFM4-sh group.

    BMB Rep, 2015, 48(11):630-5. PF-00562271 Besylate purchased from Selleck.

Purity & Quality Control

Choose Selective FAK Inhibitors

Biological Activity

Description PF-00562271 Besylate (PF-562271) 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 Besylate 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 NHn0fmNIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M3PsbGlvcGmkaYTpc44hd2ZiaIXtZY4hVVZvND2xNUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVAvOjd4NjFOwG0> MY\TRW5ITVJ?
human SW982 cell NV7TNHNGT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MnHPTY5pcWKrdHnvckBw\iCqdX3hckBUXzl6MjDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUCuN|I5OiEQvF2= MorUV2FPT0WU
human KM12 cell M4KxeWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NXLEclByUW6qaXLpeIlwdiCxZjDoeY1idiCNTUGyJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE4{QDV3NzFOwG0> MULTRW5ITVJ?
human COLO-205 cell MYXHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NELidYtKdmirYnn0bY9vKG:oIHj1cYFvKEORTF:tNlA2KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC52OE[1PEDPxE1? MXLTRW5ITVJ?
human COLO-829 cell M1vzeWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M1m3dGlvcGmkaYTpc44hd2ZiaIXtZY4hS0:OTz24Nlkh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0xNjd4MUe2JO69VQ>? MUHTRW5ITVJ?
human MG-63 cell MmrmS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NGK4eXRKdmirYnn0bY9vKG:oIHj1cYFvKE2JLU[zJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NE45ODZ|NzFOwG0> MkTRV2FPT0WU
human IGROV-1 cell NXzWOGdXT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NVLQN|NNUW6qaXLpeIlwdiCxZjDoeY1idiCLR2LPWk0yKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OC56MUCzPEDPxE1? NWrS[plzW0GQR1XS
human NCI-H650 cell NYrqVoZOT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NUHHc|h[UW6qaXLpeIlwdiCxZjDoeY1idiCQQ1mtTFY2OCClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTBwOEOxOVQh|ryP MYjTRW5ITVJ?
human RT-112 cell MoD4S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NVTJWZJFUW6qaXLpeIlwdiCxZjDoeY1idiCUVD2xNVIh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0xNjl6NE[g{txO MXrTRW5ITVJ?
human BCPAP cell NGnzbJhIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MUHJcohq[mm2aX;uJI9nKGi3bXHuJGJEWEGSIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MT6wNVI5QCEQvF2= M{i2[nNCVkeHUh?=
ALL-PO cell NHnMNnpIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MWPJcohq[mm2aX;uJI9nKGi3bXHuJGFNVC2STzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGuNFE2QDRizszN MnvyV2FPT0WU
human KYSE-270 cell NVLpW2VUT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M3jVRmlvcGmkaYTpc44hd2ZiaIXtZY4hU1mVRT2yO|Ah[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yNjB2N{G0JO69VQ>? MX;TRW5ITVJ?
human 8305C cell MWfHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NEHXOGhKdmirYnn0bY9vKG:oIHj1cYFvKDh|MEXDJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU4xQTlyNDFOwG0> MofNV2FPT0WU
NCI-H810 cell MYDHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MluwTY5pcWKrdHnvckBw\iCqdX3hckBPS0lvSEixNEBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvOTB5N{[g{txO M3K5[nNCVkeHUh?=
human CAL-33 cell NHP4VmFIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MWfJcohq[mm2aX;uJI9nKGi3bXHuJGNCVC1|MzDj[YxtKGe{b4f0bEBqdiCjIHPlcIwhfmmjYnnsbZR6KGG|c3H5MEBKSzVyPUGuNVI6OzhizszN M1TtWHNCVkeHUh?=
human AN3-CA cell MUXHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MonZTY5pcWKrdHnvckBw\iCqdX3hckBCVjNvQ1GgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlIyQDZ5IN88US=> NXvmVpdsW0GQR1XS
human NKM-1 cell MV\Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M4rGTGlvcGmkaYTpc44hd2ZiaIXtZY4hVkuPLUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlI4PTB4IN88US=> NFn5dGxUSU6JRWK=
human BPH-1 cell M17udmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M1jSd2lvcGmkaYTpc44hd2ZiaIXtZY4hSlCKLUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlI5PzZ4IN88US=> MUXTRW5ITVJ?
human MES-SA cell MoflS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NFT2VVJKdmirYnn0bY9vKG:oIHj1cYFvKE2HUz3TRUBk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvOzB4OEKg{txO NH;VU3VUSU6JRWK=
human CAL-62 cell MYrHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NVr6fXI5UW6qaXLpeIlwdiCxZjDoeY1idiCFQVytOlIh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yNjNzOUC5JO69VQ>? MkTrV2FPT0WU
human KYSE-150 cell MnSxS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NGf1XHJKdmirYnn0bY9vKG:oIHj1cYFvKEu\U1WtNVUxKGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:OS5|NUKzOkDPxE1? NUSxTGc{W0GQR1XS
human SK-UT-1 cell M2fXZWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MnrmTY5pcWKrdHnvckBw\iCqdX3hckBUUy2XVD2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU41PDZ2NzFOwG0> MVTTRW5ITVJ?
human HUTU-80 cell NEDNTJdIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NELU[4FKdmirYnn0bY9vKG:oIHj1cYFvKEiXVGWtPFAh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yNjR2OEi2JO69VQ>? NGjYcYtUSU6JRWK=
human SIG-M5 cell NHjGeJlIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NVLSSJh4UW6qaXLpeIlwdiCxZjDoeY1idiCVSVetUVUh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yNjR6NEi3JO69VQ>? M1XTSXNCVkeHUh?=
human AGS cell MkjxS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M{O0OWlvcGmkaYTpc44hd2ZiaIXtZY4hSUeVIHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MT61NlEzPCEQvF2= MWfTRW5ITVJ?
human ST486 cell Mlm2S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M2P1[GlvcGmkaYTpc44hd2ZiaIXtZY4hW1R2OE[gZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlU{Ojd6IN88US=> NXPRUZF5W0GQR1XS
human HSC-2 cell NEnIU4JIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MXnJcohq[mm2aX;uJI9nKGi3bXHuJGhUSy1{IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MT61N|k2KM7:TR?= NF6zVW9USU6JRWK=
human BC-1 cell Ml7IS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NF;ScldKdmirYnn0bY9vKG:oIHj1cYFvKEKFLUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlYyPjZ2IN88US=> M4nIfHNCVkeHUh?=
human CGTH-W-1 cell NY\TRYVsT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MUHJcohq[mm2aX;uJI9nKGi3bXHuJGNIXEhvVz2xJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9NU43OTZ5OTFOwG0> NWTKfIYxW0GQR1XS
human MZ1-PC cell MmXvS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NHTuS29KdmirYnn0bY9vKG:oIHj1cYFvKE2cMT3QR{Bk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVEvPjJ|MUKg{txO MkPTV2FPT0WU
human SW1710 cell NFLaS2lIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NUDlVolmUW6qaXLpeIlwdiCxZjDoeY1idiCVV{G3NVAh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0yNjZ{NkK4JO69VQ>? MnvJV2FPT0WU
human EW-13 cell M1TFNGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MYPJcohq[mm2aX;uJI9nKGi3bXHuJGVYNTF|IHPlcIwh\3Kxd4ToJIlvKGFiY3XscEB3cWGkaXzpeJkh[XO|YYmsJGlEPTB;MT62N|Q3PiEQvF2= MWfTRW5ITVJ?
human U251 cell Ml\iS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NEnEO4pKdmirYnn0bY9vKG:oIHj1cYFvKFV{NUGgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2xMlc1ODNzIN88US=> MlTXV2FPT0WU
human NCI-H460 cell MV7Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M3;jUmlvcGmkaYTpc44hd2ZiaIXtZY4hVkOLLVi0OlAh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0zNjB2OEO5JO69VQ>? NFjUTWtUSU6JRWK=
human DU-4475 cell NH3Db4JIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NVPpbGJoUW6qaXLpeIlwdiCxZjDoeY1idiCGVT20OFc2KGOnbHyg[5Jwf3SqIHnuJIEh[2WubDD2bYFjcWyrdImgZZN{[XluIFnDOVA:Oi5zNEe1PUDPxE1? Mn7QV2FPT0WU
human MFE-296 cell NXHtS3FYT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NIPFXXJKdmirYnn0bY9vKG:oIHj1cYFvKE2IRT2yPVYh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0zNjR5N{myJO69VQ>? MkDLV2FPT0WU
human DU-145 cell NVjTbmR6T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MnvSTY5pcWKrdHnvckBw\iCqdX3hckBFXS1zNEWgZ4VtdCCpcn;3eIghcW5iYTDj[YxtKH[rYXLpcIl1gSCjc4PhfUwhUUN3ME2yMlQ6OTF6IN88US=> M4rpbXNCVkeHUh?=
human MDA-MB-231 cell MVnHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M1TCZmlvcGmkaYTpc44hd2ZiaIXtZY4hVUSDLV3CMVI{OSClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTJwNEm1O|Ih|ryP MlToV2FPT0WU
human SNU-387 cell NEHtSZlIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M1TnPWlvcGmkaYTpc44hd2ZiaIXtZY4hW06XLUO4O{Bk\WyuIHfyc5d1cCCrbjDhJINmdGxidnnhZoltcXS7IHHzd4F6NCCLQ{WwQVIvPTJ6MjFOwG0> NVzicVNuW0GQR1XS

... 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]

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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]

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  • 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]

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  • Animal Models: PC-3M, BT474, BxPc3, LoVo, U87MG, H125 and H460 cells are injected s.c. into the right flank of athymic female mice .
  • 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(Data is from Selleck tests instead of citations):
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
Smiles CN(C1=C(C=CC=N1)CNC2=NC(=NC=C2C(F)(F)F)NC3=CC4=C(C=C3)NC(=O)C4)S(=O)(=O)C.C1=CC=C(C=C1)S(=O)(=O)O

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00666926 Completed Drug: PF00562271 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.

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    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.

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