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STING 作为药物发现的新兴治疗靶点:来自全球专利全景的视角。

STING as an emerging therapeutic target for drug discovery: Perspectives from the global patent landscape.

机构信息

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China; Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao 999078, China.

Warshel Institute for Computational Biology, The Chinese University of Hong Kong-Shenzhen, Shenzhen 518172, China; School of Life and Health Sciences, The Chinese University of Hong Kong-Shenzhen, Shenzhen 518172, China; School of Computer Science and Technology, University of Science and Technology of China, Hefei 230027, China.

出版信息

J Adv Res. 2023 Feb;44:119-133. doi: 10.1016/j.jare.2022.05.006. Epub 2022 May 27.

Abstract

BACKGROUND

The STimulator of INterferon Genes (STING) plays an essential role in the innate immune system by inducing the expression of type I interferons (IFNs) and inflammatory cytokines upon sensing cytosolic DNA. Although modulating STING has shown promise as a potential treatment for cancers and inflammatory and autoimmune diseases in substantial pre-clinical studies, current preliminary clinical results of STING agonists have demonstrated limited anti-tumor efficacy. Currently, there is ongoing R&D targeting STING and focusing on the delivery of next-generation therapeutics. Whereas no comprehensive analysis on the STING patent landscape has been conducted to fill the gap between basic research progress and drug development and commercialization.

AIM OF REVIEW

This study summarized the current agents in the clinical stage and global patenting profiles to help identify the current status, development trends, and emerging technologies of the nascent field of STING modulation.

KEY SCIENTIFIC CONCEPTS OF REVIEW

Rapidly increasing R&D efforts and outcomes targeting STING were indicated by the recently increasing number and pharmacologic classes of drug candidates in clinic as well as in emergent technological patenting activities. Despite the overall fragmental ownership of patents, several pioneers that have advanced the clinical evaluation of novel STING agonists have established the basis of STING-relevant inventions through their influential patents in the field. These patents also facilitated progress on novel STING modulators, relevant delivery systems, pharmaceutical compositions, and combination strategies with the potential for further enhancing therapeutic outcomes by targeting STING.

摘要

背景

STimulator of INterferon Genes(STING)在先天免疫系统中发挥着重要作用,通过在感知细胞溶质 DNA 时诱导 I 型干扰素(IFNs)和炎症细胞因子的表达。尽管在大量的临床前研究中,调节 STING 已显示出作为癌症和炎症性及自身免疫性疾病的潜在治疗方法的潜力,但目前 STING 激动剂的初步临床结果表明其抗肿瘤疗效有限。目前,正在针对 STING 进行研发,重点是开发下一代治疗药物。然而,为了填补基础研究进展与药物开发和商业化之间的空白,尚未对 STING 专利领域进行全面分析。

综述目的

本研究总结了处于临床阶段的现有药物和全球专利概况,以帮助确定 STING 调节领域的当前状况、发展趋势和新兴技术。

综述关键科学概念

通过最近在临床和新兴技术专利活动中不断增加的候选药物数量和药理学分类,表明针对 STING 的研发工作和成果正在迅速增加。尽管专利总体上碎片化,但一些先驱者通过其在该领域具有影响力的专利,为新型 STING 激动剂的临床评估奠定了基础。这些专利还推动了新型 STING 调节剂、相关递药系统、药物组合物以及与 STING 靶向联合的策略的进展,具有通过靶向 STING 进一步提高治疗效果的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e1c/9936525/7ac4413228bb/ga1.jpg

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