Estrada Anthony A, Sweeney Zachary K
Department of Discovery Chemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
J Med Chem. 2015 Sep 10;58(17):6733-46. doi: 10.1021/acs.jmedchem.5b00261. Epub 2015 May 14.
There is an urgent need for the development of Parkinson's disease (PD) treatments that can slow disease progression. The leucine-rich repeat kinase 2 (LRRK2) protein has been genetically and functionally linked to PD, and modulation of LRRK2 enzymatic activity has been proposed as a novel therapeutic strategy. In this review, we describe the bioactivity of selected small molecules that have been used to inhibit LRRK2 kinase activity in vitro or in vivo. These compounds are important tools for understanding the cellular biology of LRRK2 and for evaluating the potential of LRRK2 inhibitors as disease-modifying PD therapies.
迫切需要开发能够减缓帕金森病（PD）病情进展的治疗方法。富含亮氨酸重复激酶2（LRRK2）蛋白在基因和功能上与PD相关联，调节LRRK2酶活性已被提议作为一种新的治疗策略。在这篇综述中，我们描述了已用于在体外或体内抑制LRRK2激酶活性的特定小分子的生物活性。这些化合物是理解LRRK2细胞生物学以及评估LRRK2抑制剂作为改变疾病的PD疗法潜力的重要工具。
