Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa 388421, Anand, Gujarat, India.
Department of Polymer Science, North Carolina State University, North Carolina, USA.
Med Chem. 2022;18(7):757-771. doi: 10.2174/1573406418666220215122136.
Parkinson's disease is a relatively common neurological disorder with incidence increasing with age. Since current medications only relieve the symptoms and do not change the course of the disease, therefore, finding disease-modifying therapies is a critical unmet medical need. However, significant progress in understanding how genetics underpins Parkinson's disease (PD) has opened up new opportunities for understanding disease pathogenesis and identifying possible therapeutic targets. One such target is leucine-rich repeat kinase 2 (LRRK2), an elusive enzyme implicated in both familial and idiopathic PD risk. As a result, both academia and industry have promoted the development of potent and selective inhibitors of LRRK2. In this review, we have summarized recent progress in the discovery and development of LRKK2 inhibitors as well as the bioactivity of several small-molecule LRRK2 inhibitors that have been used to inhibit LRRK2 kinase activity in vitro or in vivo.
帕金森病是一种相对常见的神经退行性疾病，其发病率随着年龄的增长而增加。由于目前的药物只能缓解症状，不能改变疾病的进程，因此，寻找疾病修饰疗法是一个亟待满足的医学需求。然而，对遗传学如何影响帕金森病（PD）的理解的显著进展为理解疾病发病机制和确定可能的治疗靶点开辟了新的机会。LRRK2 就是这样一个靶点，它是一种在家族性和特发性 PD 风险中都有牵连的难以捉摸的酶。因此，学术界和工业界都在推动开发强效和选择性的 LRRK2 抑制剂。在这篇综述中，我们总结了 LRRK2 抑制剂的发现和开发的最新进展，以及几种已被用于抑制 LRRK2 激酶活性的体外或体内的小分子 LRRK2 抑制剂的生物活性。
