LX-039

LX-039 is a highly potent, selective and orally active estrogen receptor degrader with EC50 value of 2.29 nM. LX-039 has indole C-3 chlorine atom. LX-039 exhibits excellent mouse pharmacokinetics, low clearance, high Cmax and oral exposure. LX-039 has anti-tumor activity[1].

Signaling Pathways >> Others >> Estrogen Receptor/ERR

Research Areas >> Cancer

Estrogen receptor:2.29 nM (EC50)

LX-039 (2.5 mg/kg; PO and IV; single) exhibits excellent mouse pharmacokinetics, low clearance, high Cmax and oral exposure[1]. LX-039 (6.5 mg/kg, 20 mg/kg and 60 mg/kg; PO; daily for 21 days) inhibits tumor growth in a dose-dependent manner[1]. LX-039 (1 mg/kg; PO and IV; single) displays a moderate to low clearance (Cl) plus good oral bioavailability (F%) in both rat and dog[1]. Pharmacokinetic Parameters of LX-039 in CD-1 mouse[1]. IV PO (2.5 mg/kg) Vd (L/kg) 0.5 CL (mL/min/kg) 1.4 Cmax (nM) 1873 AUC0-24 (nM·h) 15329 F (%) 60.1 Pharmacokinetic Parameters of LX-039 in SD rat and Beagle dog[1]. SD Rat Beagle Dog Vd (L/kg, iv) 2 0.42 CL (mL/min/kg, iv) 7.7 0.84 C0, iv (nM), 1 mg/kg 2610 12800 AUC0-24, iv (nM·h), 1 mg/kg 4820 43800 Cmax, po (nM), 1 mg/kg 381 2550 AUC0-24, po (nM·h), 1 mg/kg 2700 24200 F (%) 56 55

[1]. Lu J, Chan CC, Sun D, et al. Discovery and preclinical profile of LX-039, a novel indole-based oral selective estrogen receptor degrader (SERD). Bioorg Med Chem Lett. 2022;66:128734.