ARV-471

ARV-471 is a proteolysis-targeting chimera (PROTAC) containing a derivative of the estrogen receptor (ER) modulator lasofoxifene conjugated to the immunomodulatory cereblon ligand lenalidomide (Cay-14643). It induces degradation of ER in MCF-7 breast cancer cells with a half-maximal degradation concentration (DC50) value of 0. nM. ARV-471 also induces degradation of ER in cells expressing a variety of clinically relevant ER mutants. It inhibits the growth of T47D triple-negative breast cancer cells and MCF-7 cells expressing wild-type ER (GI50s = 4. and 3. nM, respectively) and T47D cells expressing ERY537S or ERD538G hormone-independent activating mutations (GI50s = 8 and 5. nM, respectively). ARV-471 (3, 10, and 30 mg/kg per day) reduces tumor growth in an MCF-7 orthotopic mouse xenograft model. It induces tumor regression in a patient-derived xenograft (PDX) ERY537S-expressing mouse model of breast cancer when administered at doses of 10 and 30 mg/kg.. Solulibility: H2O: Slightly soluble: 0.1-1 mg/ml: .