Discovery of Potent, Selective, CNS-Penetrant Macrocyclic LRRK2 Inhibitors for the Treatment of Parkinson’s Disease

Journal of Medicinal Chemistry 2026

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Authors: Elsie C. Yu, Hua Zhou, Xin Cindy Yan, Kaitlyn M. Logan, D. Li, Anmol Gulati, Kelsey E. Poremba, Michael J. Ardolino, Jing Su, Dong Xiao, R.L. Palte, Spencer E. McMinn
+17 more Lisa M. Nogle, Donovon A. Adpressa, Samantha A. Burgess, Tina Xiong, Karin M. Otte, Harry R. Chobanian, Alan S. Bass, Susi Lee, Kara M. Pearson, Eric Messina, Michael Parisi, John E. Barnum, Zhanna Sobol, Paul J. Ciaccio, Erin F. DiMauro, Matthew J. Fell, Peter H. Fuller
DOI: 10.1021/acs.jmedchem.6c00238
Cited by: 1
References: 65

Abstract

. This macrocycle boasts a remarkably low projected human QD dose, is nongenotoxic, and achieved encouraging brain penetration in early preclinical models.

Fields of Study & Subjects

Parkinson's Disease Mechanisms and Treatments Melanoma and MAPK Pathways Nuclear Receptors and Signaling

Publication details

Journal / source
Journal of Medicinal Chemistry
Publisher
American Chemical Society (ACS)
Volume
69
Issue
7
Pages
8548–8560
Publication date
30 March 2026
Language
EN