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XL01126
- Development stage
- Preclinical
- Lead developer
- University of Dundee
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
- Administration
- Oral, Parenteral
01
Overview
XL01126 is a blood-brain barrier-permeable, selective proteolysis-targeting chimera (PROTAC) designed to degrade leucine-rich repeat kinase 2 (LRRK2). Developed by researchers at the University of Dundee's Centre for Targeted Protein Degradation (CeTPD) and MRC Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU), XL01126 consists of the LRRK2 inhibitor HG-10-102-01 linked to the von Hippel-Lindau (VHL) E3 ligase ligand VH101. It forms a cooperative ternary complex with VHL and LRRK2, leading to the polyubiquitination and proteasomal degradation of LRRK2. XL01126 is orally bioavailable and brain-penetrant, making it a valuable research tool for studying LRRK2 biology and a promising starting point for therapeutic development in Parkinson's disease.
- Other names
- LRRK2 PROTACLRRK-2 PROTACLRRK 2 PROTACXL 01126XL01126XL-01126
02
Targets
LRRK2 (Leucine-rich repeat serine/threonine-protein kinase 2)VHL (Von Hippel–Lindau tumor suppressor protein)
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