scholarly journals Discovery of a Lead Brain‐Penetrating Gonadotropin‐Releasing Hormone Receptor Antagonist with Saturable Binding in Brain

ChemMedChem ◽  
2020 ◽  
Vol 15 (17) ◽  
pp. 1624-1628
Author(s):  
Roberto B. W. Bekker ◽  
Richard Fjellaksel ◽  
Trine Hjornevik ◽  
Syed Nuruddin ◽  
Waqas Rafique ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Hormone Receptor ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Saturable Binding ◽  
Gonadotropin Releasing Hormone Receptor

scholarly journals Gonadotropin-Releasing Hormone Receptor Antagonist Mono- and Combination Therapy With Estradiol/Norethindrone Acetate Add-Back: Pharmacodynamics and Safety of OBE2109

2017 ◽  
Vol 103 (2) ◽  
pp. 497-504 ◽  
Author(s):  
Oliver Pohl ◽  
Line Marchand ◽  
Neil Fawkes ◽  
Jean-Pierre Gotteland ◽  
Ernest Loumaye
Keyword(s):  
Receptor Antagonist ◽  
Hormone Receptor ◽  
Vaginal Bleeding ◽  
Premenopausal Women ◽  
Gonadotropin Releasing Hormone ◽  
Sex Hormone ◽  
Open Label ◽  
Releasing Hormone ◽  
Gonadotropin Releasing Hormone Receptor ◽  
Norethindrone Acetate

Abstract Context OBE2109 is a potent, oral gonadotropin-releasing hormone receptor antagonist being developed for the treatment of sex-hormone–dependent diseases in women. Objective We assessed the pharmacodynamics and safety of OBE2109 alone and combined with estradiol (E2)/norethindrone acetate (NETA) add-back therapy on E2 levels and vaginal bleeding. Design, Setting, and Participants This was a single-center, open-label, randomized, parallel-group study in 76 healthy premenopausal women. Interventions Women were randomly assigned to take the following doses (in milligrams) once daily for 6 weeks: OBE2109, 100 or 200; or OBE2109/E2/NETA, 100/0.5/0.1, or 100/1.0/0.5, or 200/1.0/0.5. Main Outcome Measures E2 concentrations, bleeding pattern, exploratory bone metabolism biomarkers, and adverse events. Results OBE2109 100 mg and 200 mg alone reduced E2 levels to reach median levels of 19.5 and 3.2 pg/mL, respectively, at week 4. Median E2 levels after combined OBE2109/add-back therapy ranged between 25 and 40 pg/mL. OBE2109 100 mg or 200 mg alone induced amenorrhea. By day 15, >85% of women had no vaginal bleeding during the last 4 weeks of treatment. Add-back therapy partially impaired bleeding control: The highest amenorrhea rate (53%) was observed with OBE2109 100 mg/1.0 mg/0.5 mg. The addition of E2/NETA, particularly at 1 mg/0.5 mg, mitigated the increase of two bone markers induced by OBE2109 200 mg. Conclusion OBE2109 promptly lowered E2 levels. Add-back therapy may be required to prevent adverse effects on bone in women treated with the 200-mg dose (at 100 mg in some women). These results provide a basis for OBE2109 regimen selection to treat sex-hormone–dependent diseases.

Discovery of an Orally Bioavailable Gonadotropin-Releasing Hormone Receptor Antagonist

2016 ◽  
Vol 59 (19) ◽  
pp. 9150-9172 ◽  
Author(s):  
Seon-Mi Kim ◽  
Minhee Lee ◽  
So Young Lee ◽  
Euisun Park ◽  
Soo-Min Lee ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Hormone Receptor ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Orally Bioavailable ◽  
Gonadotropin Releasing Hormone Receptor

scholarly journals Clinical Pharmacology of Elagolix: An Oral Gonadotropin-Releasing Hormone Receptor Antagonist for Endometriosis

2019 ◽  
Vol 59 (3) ◽  
pp. 297-309 ◽  
Author(s):  
Mohamad Shebley ◽  
Akshanth R. Polepally ◽  
Ahmed Nader ◽  
Juki W. Ng ◽  
Insa Winzenborg ◽  
...  
Keyword(s):  
Clinical Pharmacology ◽  
Receptor Antagonist ◽  
Hormone Receptor ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Gonadotropin Releasing Hormone Receptor
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