TY - JOUR
T1 - Development of LRRK2 inhibitors through computational strategies
T2 - a promising avenue for Parkinson's disease
AU - Gong, Xiaoqing
AU - Tan, Shuoyan
AU - Yang, Yuwei
AU - Yu, Yang
AU - Yao, Xiaojun
AU - Liu, Huanxiang
N1 - Publisher Copyright:
© 2025 Elsevier Ltd
PY - 2025/9
Y1 - 2025/9
N2 - Parkinson's disease (PD) is a prevalent neurodegenerative disorder that remains incurable. Leucine-rich repeat kinase 2 (LRRK2) has a pivotal role in PD pathogenesis, making it a promising therapeutic target. Thus, there is an urgent need to develop structurally diverse, highly selective, blood–brain barrier (BBB)-permeable LRRK2 inhibitors. Computer-aided and artificial intelligence (AI)-driven drug design methods have shown significant advantages in the discovery of LRRK2 inhibitors. Building upon a systematic review of structural characteristics, biological functions, and molecular mechanisms of LRRK2, in this review, we summarize recent advances in LRRK2 inhibitor development, highlighting the pivotal role of computational approaches in accelerating inhibitor discovery.
AB - Parkinson's disease (PD) is a prevalent neurodegenerative disorder that remains incurable. Leucine-rich repeat kinase 2 (LRRK2) has a pivotal role in PD pathogenesis, making it a promising therapeutic target. Thus, there is an urgent need to develop structurally diverse, highly selective, blood–brain barrier (BBB)-permeable LRRK2 inhibitors. Computer-aided and artificial intelligence (AI)-driven drug design methods have shown significant advantages in the discovery of LRRK2 inhibitors. Building upon a systematic review of structural characteristics, biological functions, and molecular mechanisms of LRRK2, in this review, we summarize recent advances in LRRK2 inhibitor development, highlighting the pivotal role of computational approaches in accelerating inhibitor discovery.
KW - AI-driven drug design
KW - LRRK2 inhibitors
KW - Parkinson's disease
KW - computer-aided drug design
UR - https://www.scopus.com/pages/publications/105013092662
U2 - 10.1016/j.drudis.2025.104446
DO - 10.1016/j.drudis.2025.104446
M3 - Review article
C2 - 40769274
AN - SCOPUS:105013092662
SN - 1359-6446
VL - 30
JO - Drug Discovery Today
JF - Drug Discovery Today
IS - 9
M1 - 104446
ER -