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Purity: ≥98%
PF-562271 HCl is the hydrochloride salt of PF-562271 (PF562271 or PF 562271), which is a potent, ATP-competitive, orally bioavailable, reversible inhibitor of FAK (focal adhesion kinase) and Pyk2 (proline-rich tyrosine kinase) catalytic activity with potential anticancer activity. It inhibits FAK and Pyk2 with IC50s of 1.5 and 14 nmol/L, respectively. PF-562271 exhibits >100-fold selectivity for FAK 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 studies involving recombinant enzymes, PF-562271 (VS-6062) hydrochloride has demonstrated a 30- to 120-nM inhibitory effect on CDK2/E, CDK5/p35, CDK1/B, and CDK3/E. In assays involving cells, however, 3.3 μM PF-562271 must be exposed for 48 hours in order to modify the progression of the cell cycle. With an IC50 of 5 nM, PF-562271 demonstrates potency in an inducible cell-based assay for detecting phospho-FAK. PF -562271, a selective inhibitor of proline-rich tyrosine kinase 2 (PYK2), a member of the FAK family, and selective inhibitor of FAK, on the formation of colonies and cell proliferation in Ewing sarcoma cell lines. Using 2-fold serial dilutions, seven cell lines are treated with PF-562271 for five days at various doses. 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 |
PF-562271, when administered intraperitoneally to tumor-bearing animals, reduces FAK phosphorylation in vivo in a dose-dependent manner (calculated EC50 of 93 ng/mL, total). When PF-562271 is administered to rats for two weeks, the tumor growth slows down and there are indications of bone repair, such as the deposition of new cortical and cancellous bone at tumor-damaged sites[3].
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| References |
[1]. Roberts WG, et al. Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res, 2008, 68(6), 1935-1944.
[2]. Crompton BD, et al. High-throughput tyrosine kinase activity profiling identifies FAK as a candidate therapeutic target in Ewing sarcoma. Cancer Res. 2013 May 1;73(9):2873-83. [3]. Bagi CM, et al. Dual focal adhesion kinase/Pyk2 inhibitor has positive effects on bone tumors: implications for bone metastases. Cancer. 2008 May 15;112(10):2313-21. |
| Molecular Formula |
C21H21CLF3N7O3S
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|---|---|
| Molecular Weight |
543.95
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| CAS # |
939791-41-0
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| Related CAS # |
PF-562271;717907-75-0
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| SMILES |
CS(=O)(N(C)C1=NC=CC=C1CNC2=NC(NC3=CC4=C(NC(C4)=O)C=C3)=NC=C2C(F)(F)F)=O.[H]Cl
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| InChi Key |
RQEBZJWSAAWCAV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H20F3N7O3S.ClH/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);1H
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| Synonyms |
PF562271 HCl; PF-00562271; PF562271 hydrochloride; PF 562271; PF562271; PF-562271; PF00562271; PF 00562271; PF00562271 hydrochloride. PF271; PF-271; PF 271;
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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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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8384 mL | 9.1920 mL | 18.3840 mL | |
| 5 mM | 0.3677 mL | 1.8384 mL | 3.6768 mL | |
| 10 mM | 0.1838 mL | 0.9192 mL | 1.8384 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. 2010 Jul 1; 10(1): 38–43. |
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