PF-562271 HCl
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MedKoo CAT#: 206808

CAS#: 939791-41-0 (HCl)

Description: PF-562271, also known as VS-6062; PF-562,271, PF-271, is an orally bioavailable FAK inhibitor and The PYK2 inhibitor with potential antineoplastic and antiangiogenic activities. PF-562271 inhibits the tyrosine kinase FAK, and to a lesser extent, proline-rich tyrosine kinase (PYK2), which may inhibit tumor cell migration, proliferation, and survival.


Chemical Structure

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PF-562271 HCl
CAS# 939791-41-0 (HCl)

Theoretical Analysis

MedKoo Cat#: 206808
Name: PF-562271 HCl
CAS#: 939791-41-0 (HCl)
Chemical Formula: C21H21ClF3N7O3S
Exact Mass: 0.00
Molecular Weight: 543.950
Elemental Analysis: C, 46.37; H, 3.89; Cl, 6.52; F, 10.48; N, 18.03; O, 8.82; S, 5.89

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1350 Ready to ship
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Related CAS #: 939791-38-5 (besylate)   717907-75-0 (free base)   939791-39-6 (mesylate)   939791-41-0 (HCl)   939791-40-9 (tosylate)  

Synonym: PF562271 hydrochloride. PF562271; PF562271; PF-562271; PF562,271; PF562,271; PF-562,271; PF-00562271; PF00562271; PF 00562271; PF271, PF-271, PF 271; VS-6062; VS-6062; VS 6062;

IUPAC/Chemical Name: N-methyl-N-(3-(((2-((2-oxoindolin-5-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)pyridin-2-yl)methanesulfonamide hydrochloride

InChi Key: RQEBZJWSAAWCAV-UHFFFAOYSA-N

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

SMILES Code: 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

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: PF-562271 hydrochloride is an ATP-competitive and reversible FAK and Pyk2 kinase inhibitor with IC50s of 1.5 nM and 13 nM, respectively.
In vitro activity: Phosphorylated FAK (Y397) was highly expressed in primary human osteosarcoma tumor samples and was associated with osteosarcoma prognosis and lung metastasis. PF562271 greatly suppressed proliferation and colony formation in human osteosarcoma cell lines. In addition, treatment of osteosarcoma cell lines with PF562271 induced apoptosis and downregulated the activity of the protein kinase B/mammalian target of rapamycin pathway. PF562271 also impaired the tube formation ability of endothelial cells in vitro. Reference: Cancer Sci. 2017 Jul; 108(7): 1347–1356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497929/
In vivo activity: Mouse bone marrow-derived macrophages (BMDMs) were obtained and treated with ATP or nigericin in the presence and absence of the clinical trial-tested Pyk2/FAK dual inhibitor, PF-562271. Consistent with findings in human monocyte-derived macrophages and THP-1 cells (Fig. 1A,B), the IL-1β secretion induced by ATP or nigericin was significantly blocked by pretreatment of BMDMs with PF-562271 (Fig. 6A). Next, this study analyzed the inhibition effect of PF-562271 on MSU-induced peritonitis (Fig. 6B). In vivo, MSU induced the production of IL-1β and the recruitment of cells (e.g., Gr-1 + F4/80− neutrophils and F4/80 + monocytes and macrophages) to the peritoneal cavity. However, pretreatment with PF-562271 significantly reduced the amounts of IL-1β and the numbers of recruited cells, compared to the DMSO control (Fig. 6C,D). These results suggest that the PF-562271-induced blockade of Pyk2 and FAK signaling reduces IL-1β production and the recruitment of inflammatory cells to the peritoneal cavity, thus alleviating the inflammatory symptoms in this in vivo model. Reference: Sci Rep. 2016; 6: 36214. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087076/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 91.90

Preparing Stock Solutions

The following data is based on the product molecular weight 543.95 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Hu C, Chen X, Wen J, Gong L, Liu Z, Wang J, Liang J, Hu F, Zhou Q, Wei L, Shen Y, Zhang W. Antitumor effect of focal adhesion kinase inhibitor PF562271 against human osteosarcoma in vitro and in vivo. Cancer Sci. 2017 Jul;108(7):1347-1356. doi: 10.1111/cas.13256. Epub 2017 Jun 8. Erratum in: Cancer Sci. 2018 Nov;109(11):3663-3664. PMID: 28406574; PMCID: PMC5497929. 2. Crompton BD, Carlton AL, Thorner AR, Christie AL, Du J, Calicchio ML, Rivera MN, Fleming MD, Kohl NE, Kung AL, Stegmaier K. 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. doi: 10.1158/0008-5472.CAN-12-1944. Epub 2013 Mar 27. PMID: 23536552. 3. Chung IC, OuYang CN, Yuan SN, Li HP, Chen JT, Shieh HR, Chen YJ, Ojcius DM, Chu CL, Yu JS, Chang YS, Chen LC. Pyk2 activates the NLRP3 inflammasome by directly phosphorylating ASC and contributes to inflammasome-dependent peritonitis. Sci Rep. 2016 Oct 31;6:36214. doi: 10.1038/srep36214. PMID: 27796369; PMCID: PMC5087076. 4. Shang N, Arteaga M, Zaidi A, Cotler SJ, Breslin P, Ding X, Kuo P, Nishimura M, Zhang J, Qiu W. FAK Kinase Activity Is Required for the Progression of c-MET/β-Catenin-Driven Hepataocellular Carcinoma. Gene Expr. 2016;17(1):79-88. doi: 10.3727/105221616X691604. Epub 2016 May 2. PMID: 27142958; PMCID: PMC5064945.
In vitro protocol: 1. Hu C, Chen X, Wen J, Gong L, Liu Z, Wang J, Liang J, Hu F, Zhou Q, Wei L, Shen Y, Zhang W. Antitumor effect of focal adhesion kinase inhibitor PF562271 against human osteosarcoma in vitro and in vivo. Cancer Sci. 2017 Jul;108(7):1347-1356. doi: 10.1111/cas.13256. Epub 2017 Jun 8. Erratum in: Cancer Sci. 2018 Nov;109(11):3663-3664. PMID: 28406574; PMCID: PMC5497929. 2. Crompton BD, Carlton AL, Thorner AR, Christie AL, Du J, Calicchio ML, Rivera MN, Fleming MD, Kohl NE, Kung AL, Stegmaier K. 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. doi: 10.1158/0008-5472.CAN-12-1944. Epub 2013 Mar 27. PMID: 23536552.
In vivo protocol: 1. Chung IC, OuYang CN, Yuan SN, Li HP, Chen JT, Shieh HR, Chen YJ, Ojcius DM, Chu CL, Yu JS, Chang YS, Chen LC. Pyk2 activates the NLRP3 inflammasome by directly phosphorylating ASC and contributes to inflammasome-dependent peritonitis. Sci Rep. 2016 Oct 31;6:36214. doi: 10.1038/srep36214. PMID: 27796369; PMCID: PMC5087076. 2. Shang N, Arteaga M, Zaidi A, Cotler SJ, Breslin P, Ding X, Kuo P, Nishimura M, Zhang J, Qiu W. FAK Kinase Activity Is Required for the Progression of c-MET/β-Catenin-Driven Hepataocellular Carcinoma. Gene Expr. 2016;17(1):79-88. doi: 10.3727/105221616X691604. Epub 2016 May 2. PMID: 27142958; PMCID: PMC5064945.

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1: Ortiz-Rivera J, Nuñez R, Kucheryavykh Y, Kucheryavykh L. The PYK2 inhibitor PF-562271 enhances the effect of temozolomide on tumor growth in a C57Bl/6-Gl261 mouse glioma model. J Neurooncol. 2023 Feb;161(3):593-604. doi: 10.1007/s11060-023-04260-3. Epub 2023 Feb 15. PMID: 36790653; PMCID: PMC9992029.


2: Yu HJ, Shin JA, Cho SD. Inhibition of focal adhesion kinase/paxillin axis by caffeic acid phenethyl ester restrains aggressive behaviors of head and neck squamous cell carcinoma in vitro. Arch Oral Biol. 2023 Feb;146:105611. doi: 10.1016/j.archoralbio.2022.105611. Epub 2022 Dec 24. PMID: 36577313.


3: Zhao T, Liu B, Zhang M, Li S, Zhao C, Cheng L. Assessment of alterations in histone modification function and guidance for death risk prediction in cervical cancer patients. Front Genet. 2022 Sep 19;13:1013571. doi: 10.3389/fgene.2022.1013571. PMID: 36199574; PMCID: PMC9527294.


4: Qin Q, Wang R, Fu Q, Zhang G, Wu T, Liu N, Lv R, Yin W, Sun Y, Sun Y, Zhao D, Cheng M. Design, synthesis, and biological evaluation of potent FAK-degrading PROTACs. J Enzyme Inhib Med Chem. 2022 Dec;37(1):2241-2255. doi: 10.1080/14756366.2022.2100886. PMID: 35978496; PMCID: PMC9455338.


5: Luo W, Han Y, Li X, Liu Z, Meng P, Wang Y. Breast Cancer Prognosis Prediction and Immune Pathway Molecular Analysis Based on Mitochondria-Related Genes. Genet Res (Camb). 2022 May 31;2022:2249909. doi: 10.1155/2022/2249909. PMID: 35707265; PMCID: PMC9174003.


6: Cho H, Shin I, Yoon H, Jeon E, Lee J, Kim Y, Ryu S, Song C, Kwon NH, Moon Y, Kim S, Kim ND, Choi HG, Sim T. Identification of Thieno[3,2-d]pyrimidine Derivatives as Dual Inhibitors of Focal Adhesion Kinase and FMS-like Tyrosine Kinase 3. J Med Chem. 2021 Aug 26;64(16):11934-11957. doi: 10.1021/acs.jmedchem.1c00459. Epub 2021 Jul 29. PMID: 34324343.


7: Tan H, Liu Y, Gong C, Zhang J, Huang J, Zhang Q. Synthesis and evaluation of FAK inhibitors with a 5-fluoro-7H-pyrrolo[2,3-d]pyrimidine scaffold as anti- hepatocellular carcinoma agents. Eur J Med Chem. 2021 Nov 5;223:113670. doi: 10.1016/j.ejmech.2021.113670. Epub 2021 Jun 25. PMID: 34214842.


8: Tien (田婷怡) TY, Wu (吳懿哲) YJ, Su (蘇正煌) CH, Wang (王學孝) HH, Hsieh (謝金玲) CL, Wang (王博正) BJ, Su (蘇瑀) Y, Yeh (葉宏一) HI. Reduction of Connexin 43 Attenuates Angiogenic Effects of Human Smooth Muscle Progenitor Cells via Inactivation of Akt and NF-κB Pathway. Arterioscler Thromb Vasc Biol. 2021 Feb;41(2):915-930. doi: 10.1161/ATVBAHA.120.315650. Epub 2020 Dec 24. PMID: 33356390.


9: Shi Y, Bray W, Smith AJ, Zhou W, Calaoagan J, Lagisetti C, Sambucetti L, Crews P, Lokey RS, Webb TR. An exon skipping screen identifies antitumor drugs that are potent modulators of pre-mRNA splicing, suggesting new therapeutic applications. PLoS One. 2020 May 29;15(5):e0233672. doi: 10.1371/journal.pone.0233672. PMID: 32469945; PMCID: PMC7259758.


10: Fenelon JC, Xu B, Baltz JM. Focal adhesion kinase PTK2 autophosphorylation is not required for the activation of sodium-hydrogen exchange by decreased cell volume in the preimplantation mouse embryo. Zygote. 2019 Jun;27(3):173-179. doi: 10.1017/S0967199419000212. Epub 2019 Jun 7. PMID: 31171046.


11: Hong KO, Ahn CH, Yang IH, Han JM, Shin JA, Cho SD, Hong SD. Norcantharidin Suppresses YD-15 Cell Invasion Through Inhibition of FAK/Paxillin and F-Actin Reorganization. Molecules. 2019 May 19;24(10):1928. doi: 10.3390/molecules24101928. PMID: 31109130; PMCID: PMC6572169.


12: Al-Ghabkari A, Qasrawi DO, Alshehri M, Narendran A. Focal adhesion kinase (FAK) phosphorylation is a key regulator of embryonal rhabdomyosarcoma (ERMS) cell viability and migration. J Cancer Res Clin Oncol. 2019 Jun;145(6):1461-1469. doi: 10.1007/s00432-019-02913-3. Epub 2019 Apr 21. PMID: 31006845.


13: Wang S, Hwang EE, Guha R, O'Neill AF, Melong N, Veinotte CJ, Conway Saur A, Wuerthele K, Shen M, McKnight C, Alexe G, Lemieux ME, Wang A, Hughes E, Xu X, Boxer MB, Hall MD, Kung A, Berman JN, Davis MI, Stegmaier K, Crompton BD. High- throughput Chemical Screening Identifies Focal Adhesion Kinase and Aurora Kinase B Inhibition as a Synergistic Treatment Combination in Ewing Sarcoma. Clin Cancer Res. 2019 Jul 15;25(14):4552-4566. doi: 10.1158/1078-0432.CCR-17-0375. Epub 2019 Apr 12. PMID: 30979745; PMCID: PMC6634997.


14: Chi Q, Wang L, Xie D, Wang X. Characterization of in vitro metabolism of focal adhesion kinase inhibitors by LC/MS/MS. J Pharm Biomed Anal. 2019 May 10;168:163-173. doi: 10.1016/j.jpba.2019.02.028. Epub 2019 Feb 19. PMID: 30807921.


15: Xiang M, Luo H, Wu J, Ren L, Ding X, Wu C, Chen J, Chen S, Zhang H, Yu L, Zou Y, Xu H, Ye P, Chen M, Xia J. ADAM23 in Cardiomyocyte Inhibits Cardiac Hypertrophy by Targeting FAK - AKT Signaling. J Am Heart Assoc. 2018 Sep 18;7(18):e008604. doi: 10.1161/JAHA.118.008604. PMID: 30371220; PMCID: PMC6222933.


16: Wang Y, Zheng J, Han Y, Zhang Y, Su L, Hu D, Fu X. JAM-A knockdown accelerates the proliferation and migration of human keratinocytes, and improves wound healing in rats via FAK/Erk signaling. Cell Death Dis. 2018 Aug 28;9(9):848. doi: 10.1038/s41419-018-0941-y. PMID: 30154481; PMCID: PMC6113279.


17: Liu NG, Yu JN, Hu B, Guo Y, Guo CQ. [Phosphorylated Focal Adhesion Kinase, Phosphinositides 3 Kinase and Aggrecan Genes and Proteins in Cartilage Cells Are Probably Involved in Needle Knife Intervention Induced Improvement of Knee Osteoarthritis in Rabbits]. Zhen Ci Yan Jiu. 2018 Apr 25;43(4):221-5. Chinese. doi: 10.13702/j.1000-0607.170890. PMID: 29888574.


18: Fang Y, Wang D, Xu X, Dava G, Liu J, Li X, Xue Q, Wang H, Zhang J, Zhang H. Preparation, in vitro and in vivo evaluation, and molecular dynamics (MD) simulation studies of novel F-18 labeled tumor imaging agents targeting focal adhesion kinase (FAK). RSC Adv. 2018 Mar 14;8(19):10333-10345. doi: 10.1039/c8ra00652k. PMID: 35540451; PMCID: PMC9078890.


19: Ali D, Abuelreich S, Alkeraishan N, Shwish NB, Hamam R, Kassem M, Alfayez M, Aldahmash A, Alajez NM. Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells. Biosci Rep. 2018 Jan 30;38(1):BSR20171252. doi: 10.1042/BSR20171252. PMID: 29298881; PMCID: PMC5789155.


20: Mazzu YZ, Hu Y, Soni RK, Mojica KM, Qin LX, Agius P, Waxman ZM, Mihailovic A, Socci ND, Hendrickson RC, Tuschl T, Singer S. miR-193b-Regulated Signaling Networks Serve as Tumor Suppressors in Liposarcoma and Promote Adipogenesis in Adipose-Derived Stem Cells. Cancer Res. 2017 Nov 1;77(21):5728-5740. doi: 10.1158/0008-5472.CAN-16-2253. Epub 2017 Sep 7. PMID: 28882999.

1. Murphy JM, Jeong K, Cioffi DL, Campbell PM, Jo H, Ahn EE, Lim SS. Focal Adhesion Kinase Activity and Localization is Critical for TNF-α-Induced Nuclear Factor-κB Activation. Inflammation. 2021 Feb 2. doi: 10.1007/s10753-020-01408-5. Epub ahead of print. PMID: 33527321.

2. Ortiz-Rivera J, Nuñez R, Kucheryavykh Y, Kucheryavykh L. The PYK2 inhibitor PF-562271 enhances the effect of temozolomide on tumor growth in a C57Bl/6-Gl261 mouse glioma model. J Neurooncol. 2023 Feb;161(3):593-604. doi: 10.1007/s11060-023-04260-3. Epub 2023 Feb 15. PMID: 36790653; PMCID: PMC9992029.

3. Rolón-Reyes K, Kucheryavykh YV, Cubano LA, Inyushin M, Skatchkov SN, Eaton MJ, Harrison JK, Kucheryavykh LY. Microglia Activate Migration of Glioma Cells through a Pyk2 Intracellular Pathway. PLoS One. 2015 Jun 22;10(6):e0131059. doi: 10.1371/journal.pone.0131059. PMID: 26098895; PMCID: PMC4476590.

4. Lu H, Wang L, Gao W, Meng J, Dai B, Wu S, Minna J, Roth JA, Hofstetter WL, Swisher SG, Fang B. IGFBP2/FAK pathway is causally associated with dasatinib resistance in non-small cell lung cancer cells. Mol Cancer Ther. 2013 Dec;12(12):2864-73. doi: 10.1158/1535-7163.MCT-13-0233. Epub 2013 Oct 15. PMID: 24130049; PMCID: PMC3858413.

5. Kuonen F, Surbeck I, Sarin KY, Dontenwill M, Rüegg C, Gilliet M, Oro AE, Gaide O. TGFβ, Fibronectin and Integrin α5β1 Promote Invasion in Basal Cell Carcinoma. J Invest Dermatol. 2018 Nov;138(11):2432-2442. doi: 10.1016/j.jid.2018.04.029. Epub 2018 Jul 14. PMID: 29758283; PMCID: PMC6207534.

6. Gao C, Chen G, Kuan SF, Zhang DH, Schlaepfer DD, Hu J. FAK/PYK2 promotes the Wnt/β-catenin pathway and intestinal tumorigenesis by phosphorylating GSK3β. Elife. 2015 Sep 3;4:e10072. doi: 10.7554/eLife.10072. PMID: 26274564; PMCID: PMC4558782.

7. Chen G, Gao C, Gao X, Zhang DH, Kuan SF, Burns TF, Hu J. Wnt/β-Catenin Pathway Activation Mediates Adaptive Resistance to BRAF Inhibition in Colorectal Cancer. Mol Cancer Ther. 2018 Apr;17(4):806-813. doi: 10.1158/1535-7163.MCT-17-0561. Epub 2017 Nov 22. PMID: 29167314; PMCID: PMC5882543.

8. Jeong K, Murphy JM, Rodriguez YAR, Kim JS, Ahn EE, Lim SS. FAK inhibition reduces metastasis of α4 integrin-expressing melanoma to lymph nodes by targeting lymphatic VCAM-1 expression. Biochem Biophys Res Commun. 2019 Feb 19;509(4):1034-1040. doi: 10.1016/j.bbrc.2019.01.050. Epub 2019 Jan 17. PMID: 30660359; PMCID: PMC6350924.

9. Murphy JM, Jeong K, Rodriguez YAR, Kim JH, Ahn EE, Lim SS. FAK and Pyk2 activity promote TNF-α and IL-1β-mediated pro-inflammatory gene expression and vascular inflammation. Sci Rep. 2019 May 20;9(1):7617. doi: 10.1038/s41598-019-44098-2. PMID: 31110200; PMCID: PMC6527705.

10. Kim JS, Lim SS. LED Light-Induced ROS Differentially Regulates Focal Adhesion Kinase Activity in HaCaT Cell Viability. Curr Issues Mol Biol. 2022 Mar 4;44(3):1235-1246. doi: 10.3390/cimb44030082. PMID: 35723305; PMCID: PMC8947587.

11. Lu H, Wang L, Gao W, Meng J, Dai B, Wu S, Minna J, Roth JA, Hofstetter WL, Swisher SG, Fang B. IGFBP2/FAK pathway is causally associated with dasatinib resistance in non-small cell lung cancer cells. Mol Cancer Ther. 2013 Dec;12(12):2864-73. doi: 10.1158/1535-7163.MCT-13-0233. Epub 2013 Oct 15. PMID: 24130049; PMCID: PMC3858413.

12. Knuchel S, Anderle P, Werfelli P, Diamantis E, Rüegg C. Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin αvβ5-mediated adhesion. Oncotarget. 2015 Jun 10;6(16):14300-17. doi: 10.18632/oncotarget.3883. PMID: 25973543; PMCID: PMC4546468.