As effective ways to regulate protein levels, targeted protein degradation technologies have attracted great attention in recent years. Here, we established a novel integrin-facilitated lysosomal degradation (IFLD) strategy to degrade extracellular and cell membrane proteins using bifunctional compounds as molecular degraders. By conjugation of a target protein-binding ligand with an integrin-recognition ligand, the resulting molecular degrader proved to be highly efficient to induce the internalization and subsequent degradation of extracellular or cell membrane proteins in an integrin- and lysosome-dependent manner. As demonstrated in the development of BMS-L1-RGD, which is an efficient programmed death-ligand 1 (PD-L1) degrader validated both in vitro and in vivo, the IFLD strategy expands the toolbox for regulation of secreted and membrane-associated proteins and thus has great potential to be applied in chemical biology and drug discovery.
Congratulations to Professor Lijing Fang and co-authors from Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences and Southern University of Science and Technology for their excellent work published in J Am Chem Soc (JACS)!
InvivoChem is proud to provide Professor Lijing Fang’s team with our high-quality product BMS-8 (Cat #: V3256; CAS #: 1675201-90-7, small molecule PD-1/PD-L1 inhibitor) and PH-002 (Cat #: V17643; CAS #: 1311174-68-1, inhibitor of apolipoprotein (apo) E4 intramolecular domain interaction) for this research.
References: J Am Chem Soc. 2022 Dec 7;144(48):21831-21836. doi: 10.1021/jacs.2c08367.