Amcenestrant

SAR439859 (compound 43d) is an orally active, nonsteroidal and selective estrogen receptor degrader (SERD). SAR439859 is a potent ER antagonsit (EC₅₀=0.2 nM), belonging to Ligands for Target Protein for PROTAC^[1]. SAR439859 demonstrates robust antitumor efficacy and limited cross-resistance in ER⁺ breast cancer^[2]. In Vitro:SAR439859 (compound 43d) induces strong in vivo antitumor activity against a variety of BC cell lines and patient-derived xenografts, including models that harbor ERα mutations^[1].
In Vivo:SAR439859 (compound 43d; orally; 2.5-25 mg/kg; twice daily for 30 days) exhibits substantial tumor-growth inhibition and displays tumor regression at the dose of 25 mg/kg/BID^[1].
SAR439859 (3 mg/kg for iv and 10 mg/kg for po) shows a low to moderate clearance in the three animal species tested (0.03-1.92 L/h kg), low to moderate volume of distribution (V_ss=0.5-6.1 L/kg), and good bioavailability (54-76%) across species. It is noticed that T_1/2 was variable across species (1.98 h in mouse, 4.13 h in rat and 9.80 h in dog)^[1].