esr1 y537s

Vepdegestrant (ARV-471) is a selective and highly potent estrogen receptor (ER, ESR1) PROTAC degrader with strong degrading activity against the ER protein. By directly degrading the ER protein rather than merely antagonizing its activity, vepdegestrant effectively inhibits the ER signaling pathway and demonstrates significant antitumor activity in ER-positive (ER⁺) breast cancer, with a DC50 value of approximately 2 nM. It is particularly effective against tumors harboring ESR1 mutations.

GLL 398 is an orally active and selective degrader of estrogen receptor with an IC50 of 1.14 nM. GLL 398 blocks tumor growth in xenograft breast cancer models.