TAK-683 is an effective full KISS1 receptor agonist (IC50=170 pM). TAK-683 is a nonapeptide metastin analog, shows agonistic activities to KISS1R (EC50: 0.96 nM and 1.6 nM for human and rat, respectively).

KISS1R:170 pM

In rat KISS1R-expressing Chinese hamster ovary cells, TAK-683 exhibits an IC50 value (95% CI) from receptor binding assays is 150-180 pM and EC50 value (95% CI) from Ca+ mobilization assays is 180 (159–203) pM [4].

TAK-683 (subcutaneous injection; 0.008, 0.08, 0.8, or 8 μmol/ml/kg; once daily; 7 days) initially increases plasma luteinizing hormone and testosterone levels, but reduces plasma hormones and genital organ weights after 7 days. In a prostate cancer model with TAK-683 (subcutaneous injection; 2.1-21 nmol/kg/day; once daily; 12 weeks), serum PSA concentrations decrease below detection levels (0.5 ng/ml) in all rats by day 14. TAK-683 (subcutaneous injection; 10, 30, or 100 pmol/h; once daily; 4 weeks) shows promise in suppressing reproductive functions and hormone-related diseases such as prostate cancer [3][4].