Relugolix

Biological Activity

Relugolix (TAK-385) possesses higher affinity and potent antagonistic activity for human (binding IC50=0.33 nM in the presence of serum) and monkey GnRH receptor (IC50=0.32 nM), but has low affinity for the rat GnRH receptor (IC50=9800 nM).

Relugolix (TAK-385) acts as an antagonist for human GnRH receptor in vivo and daily oral administration potently, continuously and reversibly suppresses the hypothalamic-pituitary-gonadal axis.

Protocol

Cell Experiment
Cell lines
Preparation method
Concentrations
Incubation time

Animal Experiment
Animal models	Six-week-old male hGNRHR-knock-in mice
Formulation	0.5% methylcellulose solution containing 6 mg/mL citric acid monohydrate
Dosages	3, 10 or 30 mg/kg
Administration	oral

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

Medical Castration Using the Investigational Oral GnRH Antagonist TAK-385 (Relugolix): Phase 1 Study in Healthy Males.
MacLean DB, et al. J Clin Endocrinol Metab. 2015 Dec;100(12):4579-87. PMID: 26502357.

Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: studies in human GnRH receptor knock-in mice.
Nakata D, et al. Eur J Pharmacol. 2014 Jan 15;723:167-74. PMID: 24333551.