PF-562271
(Synonyms: N-甲基-N-[3-[[[2-[(2-氧代-2,3-二氢-1H-吲哚-5-基)氨基]-5-三氟甲基嘧啶-4-基]氨基]甲基]吡啶-2-基]甲磺酰胺,PF562271;PF 562271) 目录号 : GC15380
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。
Cas No.:717907-75-0
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | human glioblastoma CL-2 cells |
Preparation Method | Cells were treated with 16nM PF-562271 and 100µM TMZ for 72h. Then live and dead cells were quantifed based on calcein and ethidium homodimer-1 staining for live and dead cells. |
Reaction Conditions | 16nM; 72h |
Applications | PF-562271 treatment combined with TMZ reduces cell viability in primary glioblastoma human cell lines compared to TMZ monotherapy. |
| Animal experiment [1]: | |
Animal models | C57Bl/6-GL261 mouse glioma implantation model |
Preparation Method | Beginning on the 5th day after tumor implantation, mice received 2weeks of 50mg/kg PF-562271 combined with 50mg/kg TMZ through oral gavage. Then Immunohistochemical evaluation of tumor size was performed to evaluate effect of PF-562271 on tumor growth. |
Dosage form | 50mg/kg/d; 2weeks; oral |
Applications | Combined PF-562271 and TMZ treatment reduces tumor growth in a C57BL/6 GL261 mouse model |
References: | |
| Cas No. | 717907-75-0 | SDF | |
| 别名 | N-甲基-N-[3-[[[2-[(2-氧代-2,3-二氢-1H-吲哚-5-基)氨基]-5-三氟甲基嘧啶-4-基]氨基]甲基]吡啶-2-基]甲磺酰胺,PF562271;PF 562271 | ||
| 化学名 | N-methyl-N-[3-[[[2-[(2-oxo-1,3-dihydroindol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]pyridin-2-yl]methanesulfonamide | ||
| Canonical 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 | ||
| 分子式 | C21H20F3N7O3S | 分子量 | 507.49 |
| 溶解度 | ≥ 25.35mg/mL in DMSO, ≥ 2.25 mg/mL in EtOH with ultrasonic and warming | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 | 3.941 mL |
| 10 mM | 0.197 mL | 0.9852 mL | 1.9705 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >99.50%
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