GNE-149 is an orally bioavailable full antagonist of estrogen receptor α ( ERα ; IC 50 =0.053 nM). GNE-149 is a selective estrogen receptor degrader (SERD). GNE-149 can be used for the research of breast cancer
In Vitro
GNE-149 exhibits antiproliferative activity in MCF7 and T47D cells with IC 50 s of 0.66 and 0.69 nM, respectively. GNE-149 exhibits ERα Degradation in MCF7 and T47D cells with IC 50 s of 0.053 and 0.031 nM, respectively. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
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 . 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) . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female Crl:NU Foxn1 nu mice (at 7 weeks of age) bearing wild-type (WT) ERαor overexpressed Y537S mutant MCF7 tumor 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.
