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针对 I 型 PRMTs 作为治疗肺部疾病(哮喘、COPD、肺癌、PF 和 PH)的有希望的靶点。

Targeting type I PRMTs as promising targets for the treatment of pulmonary disorders: Asthma, COPD, lung cancer, PF, and PH.

机构信息

Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.

Department of Pharmacy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

出版信息

Life Sci. 2024 Apr 1;342:122538. doi: 10.1016/j.lfs.2024.122538. Epub 2024 Feb 28.

Abstract

Pulmonary disorders, including asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), pulmonary hypertension (PH), and lung cancer, seriously impair the quality of lives of patients. A deeper understanding of the occurrence and development of the above diseases may inspire new strategies to remedy the scarcity of treatments. Type I protein arginine methyltransferases (PRMTs) can affect processes of inflammation, airway remodeling, fibroblast proliferation, mitochondrial mass, and epithelial dysfunction through substrate methylation and non-enzymatic activity, thus affecting the occurrence and development of asthma, COPD, lung cancer, PF, and PH. As potential therapeutic targets, inhibitors of type I PRMTs are developed, moreover, representative compounds such as GSK3368715 and MS023 have also been used for early research. Here, we collated structures of type I PRMTs inhibitors and compared their activity. Finally, we highlighted the physiological and pathological associations of type I PRMTs with asthma, COPD, lung cancer, PF, and PH. The developing of type I PRMTs modulators will be beneficial for the treatment of these diseases.

摘要

肺部疾病,包括哮喘、慢性阻塞性肺疾病(COPD)、肺纤维化(PF)、肺动脉高压(PH)和肺癌,严重影响患者的生活质量。深入了解这些疾病的发生和发展,可能会激发新的策略来弥补治疗方法的匮乏。I 型蛋白精氨酸甲基转移酶(PRMTs)可以通过底物甲基化和非酶活性影响炎症、气道重塑、成纤维细胞增殖、线粒体质量和上皮功能障碍等过程,从而影响哮喘、COPD、肺癌、PF 和 PH 的发生和发展。作为潜在的治疗靶点,I 型 PRMTs 的抑制剂正在被开发,此外,代表性化合物如 GSK3368715 和 MS023 也已被用于早期研究。在这里,我们整理了 I 型 PRMTs 抑制剂的结构,并比较了它们的活性。最后,我们强调了 I 型 PRMTs 与哮喘、COPD、肺癌、PF 和 PH 的生理和病理关联。I 型 PRMTs 调节剂的开发将有利于这些疾病的治疗。

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