LC3-mHTT-IN-AN1

LC3-mHTT-IN-AN1 (CAS No.: 486443-73-6) is a small-molecule autophagy-targeting chimera that functions as a mutant huntingtin (mHTT)-LC3 linker, designed to selectively promote the degradation of pathogenic huntingtin protein via the autophagy-lysosome pathway. This compound simultaneously binds microtubule-associated protein 1 light chain 3β (LC3B), a key component of autophagosomal membranes, and mHTT, while exhibiting minimal interaction with wild-type huntingtin or unrelated proteins, thereby conferring allele-selective targeting. Mechanistically, LC3-mHTT-IN-AN1 facilitates the recruitment of mHTT to autophagosomes, enhancing its clearance and reducing intracellular mHTT levels in neuronal models of Huntington’s disease. In vitro studies demonstrate activity in the nanomolar concentration range, where it effectively lowers mutant protein levels in cultured mouse neurons without affecting the wild-type counterpart. In vivo and cellular model systems, including Drosophila and murine Huntington’s disease models, show that treatment with this compound can ameliorate disease-associated phenotypes and improve survival outcomes. LC3-mHTT-IN-AN1 is widely utilized as a chemical probe for investigating selective protein degradation strategies, autophagy modulation, and neurodegenerative disease mechanisms, with experimental concentrations or dosing regimens varying depending on specific assay conditions and research objectives.