Bexirestrant is an orally active ER-α degrader commonly employed in antiestrogen and antineoplastic therapy research.

Bexirestrant (compound Formula Ia) effectively inhibits the proliferation of MCF-7 cells, regardless of their genetic background (wild type, Y537S, and D538G mutations), with IC50 values of 0.3, 6.0, and 2.2 nM, respectively[1]. Moreover, it promotes ER-α degradation in these cell lines, with IC50 values of 0.3, 19.6, and 12.7 nM, respectively[1]. Additionally, at a concentration of 1 nM, Bexirestrant results in 16.3% of ER-α remaining in wild type MCF-7 cells[1].

Bexirestrant, administered orally at a dosage of 50mg/kg for 28 days, demonstrates significant efficacy in inhibiting tumor growth by 56% in female athymic nude mice implanted with MCF7-Y537S xenografts, compared to the control group. Pharmacokinetic evaluation in rats at the same dosage reveals a maximum concentration (Cmax) of 343 ng/mL at 4 hours post-administration (Tmax), with an area under the curve (AUC) last and AUC infinity observed (AUC inf_obs) of 7582 hr×ng/mL and 9804 hr×ng/mL, respectively, and a half-life (T1/2) of 26 hours.