Synonyms: compound 32 [PMID: 30990042] | ERD308
Compound class:
Synthetic organic
Comment: ERD-308 is a small-molecule ERα degrader that was designed using the proteolysis targeting chimeras (PROTAC) model [1]. It is a hybrid molecule that links together an ERα antagonist (a derivative of raloxifene) and a VHL ligand that engages the VHL E3 ligase to direct ERα receptors for ubiquitination and proteasomal degradation.
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Bioactivity Comments |
ERD-308 induces more complete ER degradation than the approved ER degrader (SERD) fulvestrant [1] which targets ERα for proteasome-dependent degradation but via a different mechanism (protein mis-folding) to PROTACs. SERDs only achieve partial degradation of the ER protein, whereas ERD-308 can induce almost complete ER degradation at concentrations as low as 5 nM in cell lines. The DC50 of ERD-308 for ERα is 0.17 nM in MCF-7 cells, and 0.43 nM in T47D cells. It binds the VHL protein with an IC50 of 196 nM. |
Selectivity at nuclear hormone receptors | ||||||||||||||||||||||||||||||||||
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