PROTACs Degrader

LYP-8 is an intracellular nicotinamide phosphoribosyltransferase (iNAMPT) inhibitor with an IC₅₀ of 0.76 μM, a reducing agent, and a tumor growth inhibitor. LYP-8 recruits VHL E3 ligase to induce iNAMPT polyubiquitination and proteasome-dependent degradation, and inhibits iNAMPT enzymatic activity. LYP-8 reduces eNAMPT levels by degrading iNAMPT to decrease eNAMPT secretion. LYP-8 reduces intracellular NAD⁺ levels in cancer cells and proinflammatory cytokine levels (IL-6, TNF-α) in tumor tissue and serum. LYP-8 can be used for the research of colon cancer.

LC-MI-3 is an orally active IRAK4 degrader with an IC₅₀ of 57.2 nM and high selectivity among human protein kinases.LC-MI-3 eliminates IRAK4 kinase and scaffolding functions via the cereblon E3 ubiquitin ligase and ubiquitin-proteasome systems.LC-MI-3 inhibits downstream nuclear factor-κB and IRAK4-mediated inflammatory signaling pathways.LC-MI-3 exerts anti-inflammatory activity in lipopolysaccharide-, Escherichia coli-, TLR4-, and TLR7-induced inflammatory models.LC-MI-3 can be used for the research of acute lung injury, sepsis, psoriasis, and inflammatory diseases.