PF-562271 is a potent small-molecule inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) with a IC50 of 1.5 and 14nmol/L, respectively[1][2]. PF-562271 is commonly utilized in the research of various cancers, including pancreatic cancer[3], osteosarcoma and glioblastoma[4], for its potential to inhibit tumor growth and metastasis.
PF-562271 (5µM; 48h) treatment can induce apoptosis and downregulated the activity of the protein kinase B/mammalian target of rapamycin pathway in human osteosarcoma cell lines[5]. PF-562271 (16nM; 72h) treatment combined with 100µM temozolomide (TMZ) signifcantly reduces viability, cell cycle progression, invasion and invadopodia in primary human glioma cell lines[6].
PF-562271(50mg/kg) combined with TMZ enhances the effect of TMZ on tumor growth inhibition and invasiveness in C57Bl/6-GL261 mouse glioma implantation model[6]. When administered orally at a dose of 5mg/kg, PF-562271 suppressed the growth and local spread of intratibial tumors and restored tumor-induced bone loss in nude rats with MDA-MB-231 cells implanted in their tibia[7].
References:
[1]. Michael Luzzio, Christopher Autry, Martin Berliner, et al. Design, synthesis, activity and properties of selective focal adhesion kinase inhibitors which are suitable for advanced preclinical evaluation: The discovery of PF-562271. Cancer Res 1 May 2007; 67 (9_Supplement): 5432.
[2]. Roberts WG, Ung E, Whalen P, et al. Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res. 2008 Mar 15;68(6):1935-44. doi: 10.1158/0008-5472.CAN-07-5155. PMID: 18339875.
[3]. Stokes JB, Adair SJ, Slack-Davis JK, et al. Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment. Mol Cancer Ther. 2011 Nov;10(11):2135-45. doi: 10.1158/1535-7163.MCT-11-0261. Epub 2011 Sep 8. PMID: 21903606; PMCID: PMC3213273.
[4]. Ortiz Rivera J, Velez Crespo G, Inyushin M, et al. Pyk2/FAK Signaling Is Upregulated in Recurrent Glioblastoma Tumors in a C57BL/6/GL261 Glioma Implantation Model. Int J Mol Sci. 2023 Aug 30;24(17):13467. doi: 10.3390/ijms241713467. PMID: 37686276; PMCID: PMC10487692.
[5]. Hu C, Chen X, Wen J, et al. 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. doi: 10.1111/cas.13804. PMID: 28406574; PMCID: PMC5497929.
[6]. Ortiz-Rivera J, Nuñez R, Kucheryavykh Y, et al. 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.
[7]. Bagi CM, Roberts GW, Andresen CJ. Dual focal adhesion kinase/Pyk2 inhibitor has positive effects on bone tumors: implications for bone metastases. Cancer. 2008 May 15;112(10):2313-21. doi: 10.1002/cncr.23429. PMID: 18348298.
PF-562271是一种针对黏着斑激酶(FAK)和富含脯氨酸的酪氨酸激酶2(Pyk2)的强效小分子抑制剂，IC50分别为1.5nmol/L和14nmol/L[1][2]。PF-562271 具有抑制肿瘤生长和转移的潜力，被广泛用于多种癌症的研究，包括胰腺癌[3]、骨肉瘤和胶质母细胞瘤[4]。
PF-562271 (5µM，48小时)处理可在人体骨肉瘤细胞系中诱导凋亡并下调蛋白激酶B/哺乳动物雷帕霉素靶蛋白通路的活性[5]。PF-562271 (16nM，72小时)与100µM替莫唑胺(TMZ)联合使用可以显著降低初级人体胶质瘤细胞系的存活率、细胞周期进程、侵袭性及侵袭伪足[6]。
PF-562271 (50mg/kg)与TMZ联合使用在C57Bl/6-GL261小鼠胶质瘤移植模型中增强了TMZ对肿瘤生长抑制和侵袭性的效果[6]。口服给予5mg/kg剂量的PF-562271可抑制裸鼠胫骨内植入MDA-MB-231细胞后的肿瘤生长和局部扩散，并恢复肿瘤引起的骨质流失[7]。