Biological Activity
erteberel (ly500307) is a potent and selective erβ (estrogen receptor beta) agonist (ec50 = 0.66 nm). [1]estrogen receptors are nuclear hormone receptors that act as a ligand-activated transcription factor. it regulates gene expression, cell proliferation and differentiation in target tissues and involved in breast cancer, endometrial cancer and osteoporosis etc. [1]in transcription assay of cotransfected human prostate cancer cell line, erteberel showed potency (ec50 = 0.66 nm), selectivity (32-fold) and full agonist function (>90% relative efficacy) to erβ than to erα. [1]in mouse model, prostate wet weight of cd-1 mice were measured following oral daily doses of erteberel for 7 days. results showed reduction on prostate weight in a dose-dependent manner (0.01 mg/kg – 0.05 mg/kg), and no effect on testes/seminal vesicle weight and androgens testosterone/dihydrotestosterone circulating level. [1]
in vivo
Erteberel (5mg/Kg body weight/day, oral, 28 days) treatment significantly reduces tumor growth and promotes apoptosis of GBM tumors in an orthotopic model[2].
Erteberel (5mg/Kg body weight/day, oral, 40-50 days) treatment improves the overall survival of tumor-bearing mice in the GL26 syngeneic glioma model[2].
| Animal Model: | Athymic mice (5-7 weeks) inoculated with OVCAR-3 cells[2] |
| Dosage: | 5mg/Kg body weight |
| Administration: | Oral, daily for 28 days |
| Result: | Immunohistochemical analysis reveals that Erteberel treatment significantly reduces the number of proliferation marker Ki-67-positive cells and increases the number of TUNEL-positive apoptotic cells[2]. |
References
[1] norman bh, dodge ja, richardson ti, borromeo ps, lugar cw, jones sa, chen k, wang y, durst gl, barr rj, montrose-rafizadeh c, osborne he, amos rm, guo s, boodhoo a, krishnan v. benzopyrans are selective estrogen receptor beta agonists with novel activity in models of benign prostatic hyperplasia. j med chem. 2006 oct 19;49(21):6155-7.
