GNE-149

GNE-149 is an orally bioavailable full antagonist of estrogen receptor α (ERα; IC50=0.053 nM). GNE-149 is a selective estrogen receptor degrader (SERD). GNE-149 can be used for the research of breast cancer[1].

Signaling Pathways >> Others >> Estrogen Receptor/ERR

Research Areas >> Cancer

ERα:0.053 nM (IC50)

GNE-149 exhibits antiproliferative activity in MCF7 and T47D cells with IC50s of 0.66 and 0.69 nM, respectively[1]. GNE-149 exhibits ERα Degradation in MCF7 and T47D cells with IC50s of 0.053 and 0.031 nM, respectively[1].

GNE-149 (0.3-30 mg/kg) exhibits in vivo efficacy in an MCF7 xenograft mouse model harboring either wild-type (WT) ERα or overexpressed Y537S mutant[1]. GNE-149 has favorable pharmacokinetic profile, including total clearance (CL; 19, 8, and 13 mL/min/kg for Rat, Dog, and Cyno) and oral bioavailability (F; 31%, 49%, and 28% for Rat, Dog, and Cyno)[1]. Animal Model: Female Crl:NU Foxn1 nu mice (at 7 weeks of age) bearing wild-type (WT) ERαor overexpressed Y537S mutant MCF7 tumor[1] Dosage: 0.3, 1, 3, 10, and 30 mg/kg Administration: Orally q.d. for 21 days Result: Exhibited dose-dependent efficacy in the MCF7 WT and Y537S mutant xenograft model, with tumor regression observed at all doses above 0.3 mg/kg in Y537S mutant xenograft model.

[1]. Jun Liang, et al. Discovery of GNE-149 as a Full Antagonist and Efficient Degrader of Estrogen Receptor alpha for ER+ Breast Cancer. ACS Med Chem Lett. 2020 May 26;11(6):1342-1347.