Functionally active modulators targeting the LRRK2 WD40 repeat domain identified by FRASE-bot in CACHE Challenge #1
Akhila Mettu, Marta Glavatskikh, Xiaowen Wang, Antonio Jesús Lara Ordóñez, Fengling Li, Irene Chau, Suzanne Z. Ackloo, C.H. Arrowsmith, Albina Bolotokova, Pegah Ghiabi, Elisa Gibson, Levon Halabelian, Scott R. Houliston, Rachel Harding, Ashley Hutchinson, P. Loppnau, Sumera Perveen, Almagul Seitova, Hong Zeng, Matthieu Schapira · Chemical Science · 2025
) ranging from 3 to 41 μM. To investigate the functional effect of WDR ligands, they were tested for their ability to modify the LRRK2 activity markers in HEK293T cells. Two compounds showed statistically significant increases in the kinase activity of WT LRRK2, and two compounds affected the conformation and kinase activity of major LRRK2 mutants.