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Updated: Jul 10, 2025

Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation
Published on: July 16, 2014
Discovery of conformationally constrained c-Abl inhibitors with potential neuroprotective effects against Parkinson's
Zichao Yang1, Yangcheng Ai2, Guowu Wu1
1Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Abstract:
Abelson tyrosine kinase (c-Abl) is involved in various biological processes in neurodegenerative diseases and is an attractive target for anti-PD (Parkinson's disease) drug discovery. Based on our previous work, we designed several novel c-Abl inhibitors through a conformational constrained strategy and evaluated their pharmacological activities. Among them, compound A6 exhibited superior inhibitory activity against c-Abl than nilotinib in the homogenous time-resolved fluorescence (HTRF) assay. Furthermore, A6 displayed higher neuroprotective effects against SH-SY5Y cell death induced by MPP+ and lower cytotoxicity than that of nilotinib. Molecular modeling revealed that the 1H-pyrrolo[2,3-B]pyridine ring may contribute to the high affinity of A6 for binding to c-Abl. Collectively, these results suggest that A6 deserves further investigation as a c-Abl inhibitor for neurodegenerative disorders.
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