Definition

An orally bioavailable estrogen receptor (ER)-targeted chimeric protein degrader composed of ligands of ER and cereblon (CRBN) E3 ubiquitin ligase, with potential antineoplastic activity. Upon oral administration of ER degrader AC699, the ER-targeting moiety targets and binds to ER, and the CRBN-binding moiety recruits CRBN, a component of the CRL4-CRBN E3 ubiquitin ligase complex. This catalyzes ubiquitination and proteasome-mediated degradation of ER, prevents ER-mediated signaling, and inhibits both the growth and survival of ER-expressing cancer cells. ER is overexpressed in a variety of cancers and plays a key role in cancer cell proliferation.