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E3 ligase ligands bind ubiquitin ligases such as cereblon and von Hippel-Lindau (VHL) in degrader design. In a degrader, they anchor the ligase end of the molecule. E3 ubiquitin ligases transfer ubiquitin to substrate proteins and mark them for degradation by the proteasome. Thalidomide and its analogs bind cereblon (CRBN), a substrate receptor of a cullin-based E3 ligase complex identified as their direct target in 2010. The category includes cereblon ligands such as thalidomide fluoride and TD-106, and VHL ligands such as VL285 and VH032-cyclopropane-F. These ligands are used to build proteolysis-targeting chimeras (PROTACs) and to study how ligases are recruited to new substrates.
XB2M54 is a selective antagonist of X-linked inhibitor of apoptosis protein (XIAP), functioning as a ligand for E3 ligases. It effectively inhibits NOD2-mediated inflammatory signaling pathways, making it a valuable tool in inflammation research. Additionally, XB2M54 can be employed in the synthesis of PROTAC ERα Degrader-1, facilitating studies on targeted protein degradation and its implications in therapeutic applications.
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