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• W2158919946 abstract "TAK-013 is a novel nonpeptide and orally active GnRH antagonist. We first examined the effect of TAK-013 on GnRH-stimulated LH release using primary-cultured pituitary cells of cynomolgus monkeys. TAK-013 suppressed LH release to below basal levels at concentrations higher than 100 nm with the IC50 value of 36 nm. Next, we examined the effect of chronic oral administration of TAK-013 on serum hormone levels in regularly cycling female cynomolgus monkeys. TAK-013 administered at 90 mg/kg·d (30 mg/kg 3 times daily) for approximately 80 d continued to suppress LH, estradiol, and progesterone, but not FSH. The suppressive effect was reversible, in that normal profiles of sex steroids were observed immediately after discontinuation of the TAK-013 treatment. Interestingly, the suppressive effect of TAK-013 was not observed in marmoset monkeys. In summary, TAK-013 by oral administration suppresses a pituitary-ovarian axis continuously and reversibly in cynomolgus monkeys. Considering that TAK-013 has more potent antagonistic properties for human GnRH receptor than for monkey receptor, our data suggest that TAK-013 would be effective for reproductive disorders such as endometriosis and uterine leiomyoma and useful for assisted reproductive technology procedures." @default.
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• W2158919946 date "2003-04-01" @default.
• W2158919946 modified "2023-10-17" @default.
• W2158919946 title "Suppression of a Pituitary-Ovarian Axis by Chronic Oral Administration of a Novel Nonpeptide Gonadotropin-Releasing Hormone Antagonist, TAK-013, in Cynomolgus Monkeys" @default.
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• W2158919946 doi "https://doi.org/10.1210/jc.2002-021065" @default.
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