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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Review Article

Recent Update on the Development of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors: A Promising Target for the Treatment of Parkinson’s Disease

Author(s): Ashish Patel*, Stuti Patel, Meshwa Mehta, Yug Patel, Dhruv Langaliya, Shyam Bhalodiya and Tushar Bambharoliya

Volume 18, Issue 7, 2022

Published on: 31 March, 2022

Page: [757 - 771] Pages: 15

DOI: 10.2174/1573406418666220215122136

Price: $65

Abstract

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.

Keywords: Leucine-rich repeat kinase 2 (LRRK2), Parkinson's disease (PD), brain penetrant LRKK2 inhibitors, G2019SLRRK2 mutant, wild-type LRKK2, promising target.

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