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Purity: ≥98%
Description: PF-562271 is a novel, potent, ATP-competitive, orally bioavailable, reversible inhibitor of FAK (focal adhesion kinase) and Pyk2 catalytic activity with a IC50 of 1.5 and 14 nmol/L, respectively. it has >100-fold selectivity against other protein kinases. Additionally, PF-562,271 displayed robust inhibition in an inducible cell-based assay measuring phospho-FAK with an IC(50) of 5 nmol/L. PF-562,271 was evaluated against multiple kinases and displays >100x selectivity against a long list of nontarget kinases. PF-562,271 inhibits FAK phosphorylation in vivo in a dose-dependent fashion (calculated EC(50) of 93 ng/mL, total) after p.o. administration to tumor-bearing mice. In vivo inhibition of FAK phosphorylation (>50%) was sustained for >4 hours with a single p.o. dose of 33 mg/kg. Antitumor efficacy and regressions were observed in multiple human s.c. xenograft models. PF-562271 is a potential therapeutic agent either alone or in combination with other agents for the treatment of cancer.
| ln Vitro |
In recombinant enzyme assays, PF-562271 (VS-6062) is demonstrated to be a 30- to 120-nM inhibitor of CDK2/E, CDK5/p35, CDK1/B, and CDK3/E. In cell-based assays assessing the function of CDKs, 3.3 μM PF-562271 must be exposed for 48 hours in order to modify cell cycle progression. With an IC50 of 5 nM, PF-562271 demonstrates potency in an inducible cell-based assay for detecting phospho-FAK. On cell growth and colony formation in Ewing sarcoma cell lines, PF-562271, a selective inhibitor of both FAK and proline-rich tyrosine kinase 2 (PYK2), a member of the FAK-related family, acts. Using 2-fold serial dilutions, seven cell lines are treated with PF-562271 for five days at various concentrations. After three days of treatment, PF-562271 therapy reduces cell viability in all cell lines, with an average IC50 of 2.4 μM. The two most sensitive cell lines are TC32 and A673, with IC50 values of 2.1 and 1.7 μM, respectively[2].
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| ln Vivo |
Following po treatment to tumor-bearing animals, PF-562271 suppresses FAK phosphorylation in vivo in a dose-dependent manner (calculated EC50 of 93 ng/mL, total)[1]. After two weeks of treatment, rats given PF-562271 show a decrease in tumor development and indications of bone healing, as shown by the deposition of new bone (cortical and cancellous) at tumor-damaged sites[3].
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| References |
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| Additional Infomation |
N-methyl-N-[3-[[[2-[(2-oxo-1,3-dihydroindol-5-yl)amino]-5-(trifluoromethyl)-4-pyrimidinyl]amino]methyl]-2-pyridinyl]methanesulfonamide is a member of indoles.
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| Molecular Formula |
C21H20F3N7O3S
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|---|---|
| Molecular Weight |
507.4888
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| Exact Mass |
507.13
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| CAS # |
717907-75-0
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| Related CAS # |
PF-562271 besylate;939791-38-5;PF-562271 hydrochloride;939791-41-0
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| PubChem CID |
11713159
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| Appearance |
Light yellow to brown solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.645
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| LogP |
-0.71
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
856
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| Defined Atom Stereocenter Count |
0
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| SMILES |
0
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| InChi Key |
MZDKLVOWGIOKTN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H20F3N7O3S/c1-31(35(2,33)34)19-12(4-3-7-25-19)10-26-18-15(21(22,23)24)11-27-20(30-18)28-14-5-6-16-13(8-14)9-17(32)29-16/h3-8,11H,9-10H2,1-2H3,(H,29,32)(H2,26,27,28,30)
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| Chemical Name |
N-methyl-N-(3-(((2-((2-oxoindolin-5-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)pyridin-2-yl)methanesulfonamide
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| Synonyms |
PF562271; PF-562271; PF562,271; PF562,271; PF-562,271; PF-00562271; PF00562271; PF 00562271; PF271, PF-271, PF 271; PF562271 PhSO3H; PF562271 benzesulfonate salt; PF562271 besylate;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (3.29 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (3.29 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9705 mL | 9.8524 mL | 19.7048 mL | |
| 5 mM | 0.3941 mL | 1.9705 mL | 3.9410 mL | |
| 10 mM | 0.1970 mL | 0.9852 mL | 1.9705 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Efficacy of PF-562,271 in PC3M-luc-C6 subcutaneuous local implant xenograft model: PF-562,271 was administered at 25 mg/kg P.O. BID 5x/wk for two weeks.Cancer Biol Ther.2010Jul 1;10(1):38-43. |
(A) Bioluminescent image time course of a subcutaneously inoculated vehicle control mouse. PF-562,271 was administered at 25 mg/kg P.O. BID 5x/wk for two weeks. (B) Bioluminescent image time course of a subcutaneously inoculated mouse treated with PF-562,271. PF-562,271 was administered at 25 mg/kg P.O. BID 5x/wk for two weeks.Cancer Biol Ther.2010Jul 1;10(1):38-43. |
(A) Bioluminescent image time course of an intracardiac inoculated vehicle control mouse. Vehicle was administered P.O. BID 5x/wk for three weeks. (B) Bioluminescent image time course of an intracardiac inoculated treated with PF-562,271. PF-562,271 was administered at 25 mg/kg P.O. BID 5x/wk for three weeks.Cancer Biol Ther.2010Jul 1;10(1):38-43. |
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