Proteolysis targeting chimeras (PROTACs) represent a groundbreaking paradigm in drug discovery, utilizing the ubiquitin-proteasome pathway to induce the degradation of proteins of interest (POIs) by recruiting E3 ligases. Widely adopted as both biological tools and potential medicinal molecules, PROTACs hold significant promise for clinical applications. A diverse array of small molecule PROTACs has been created, with VHL-based PROTACs emerging as a particularly encouraging approach for targeting challenging proteins, including non-druggable ones like transcriptional factors and scaffold proteins. This strategy offers a novel therapeutic avenue for diseases resistant to conventional methods such as radiotherapy, chemotherapy, and small molecule inhibitors.
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