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黏着斑激酶:癌症治疗的潜在靶点。

FAK: A Potential Target for Cancer Therapy.

作者信息

Zhang Chao, Rao Yu

机构信息

Changping Laboratory, Beijing 102206, China.

State Key Laboratory of Molecular Oncology, MOE Key Laboratory of Protein Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.

出版信息

ACS Med Chem Lett. 2025 May 7;16(6):907-910. doi: 10.1021/acsmedchemlett.5c00184. eCollection 2025 Jun 12.

Abstract

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase with enzymatic and scaffolding functions, composed of a FERM domain, kinase domain, proline-rich regions, and a FAT domain. It interacts with over 50 proteins and plays a key role in cancer progression, metastasis, and recurrence. Although eight FAK inhibitors have entered clinical trials, they primarily block kinase activity and fail to disrupt scaffolding functions. PROTAC technology offers a novel strategy by degrading the entire FAK protein, eliminating both functions. Several FAK-targeting PROTACs have been developed with promising results. Given FAK's critical role in tumor malignancy, combination therapiessuch as dual-target degradation or inhibitor-degrader strategiesmay provide enhanced anticancer efficacy.

摘要

粘着斑激酶(FAK)是一种具有酶促和支架功能的非受体酪氨酸激酶,由一个FERM结构域、激酶结构域、富含脯氨酸的区域和一个FAT结构域组成。它与50多种蛋白质相互作用,在癌症进展、转移和复发中起关键作用。尽管有8种FAK抑制剂已进入临床试验,但它们主要阻断激酶活性,无法破坏支架功能。PROTAC技术提供了一种通过降解整个FAK蛋白来消除这两种功能的新策略。已经开发出几种靶向FAK的PROTAC,并取得了有前景的结果。鉴于FAK在肿瘤恶性肿瘤中的关键作用,联合治疗——如双靶点降解或抑制剂-降解剂策略——可能会提供增强的抗癌疗效。

相似文献

1
FAK: A Potential Target for Cancer Therapy.黏着斑激酶:癌症治疗的潜在靶点。
ACS Med Chem Lett. 2025 May 7;16(6):907-910. doi: 10.1021/acsmedchemlett.5c00184. eCollection 2025 Jun 12.

本文引用的文献

4
Discovery and Characterisation of Highly Cooperative FAK-Degrading PROTACs.发现并表征高度协同的 FAK 降解 PROTAC 分子。
Angew Chem Int Ed Engl. 2021 Oct 18;60(43):23327-23334. doi: 10.1002/anie.202109237. Epub 2021 Sep 17.

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