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