The human autophagy system is an important pathway for the degradation of misfolded proteins and organelles. However, approaches to target the membrane-bound autophagy modifiers (LC3/GABARAP proteins, also known as Atg8 proteins) responsible for cargo recruitment have been largely unsuccessful for decades. Therefore, our goal was to identify non-covalent small molecule ligands targeting the main binding site of LC3A (called LIR docking site (LDS)) as potential tools for autophagy modulation and targeted protein degradation (TPD). To identify new ligands, we used SeeSAR to virtually screen our in-house library, followed by biophysical pre-screening (using fluorescence polarisation) and a second iteration of screening...