LSZ102 exhibit oral bioavailability and preclinical activity as selective estrogen receptor degraders (SERDs). It is a compound in clinical development for the treatment of ERα positive breast cancer.
In Phase I/Ib trials for the treatment of ERα positive breast cancer, LSZ-102 has an IC50 of 0.2 nM. LSZ-102 induces significant degradation of ERα after 24 h, when given as a 10 μM solution to MCF-7 cells.
Treatment of the mice with LSZ102 once daily at 20 mg/kg resulted in significant tumor growth inhibition as compared to the control group treated with vehicle alone, resulting in tumor stasis (mean change in tumor volume of LSZ102 vs control = %ΔT/ΔC of 2.4% on day 48, p < 0.05).
Dosing of 3 mg/kg solution of LSZ102 in male Sprague−Dawley rats resulted in 33% bioavailability and a dose-normalized exposure of 620 nM·h
References
1. Tria GS, et al. Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer. J Med Chem. 2018 Apr 12;61(7):2837-2864.