LY-2459989
LY-2459989 is a silent antagonist of the κ-opioid receptor that has been developed by Eli Lilly as a radiotracer of the aforementioned receptor, labeled either with carbon-11 or fluorine-18. It possesses high affinity for the KOR and is highly selective for it over the μ-opioid receptor and the δ-opioid receptor . LY-2459989 is a fluorine-containing analogue and follow-up compound of LY-2795050, the first-ever KOR-selective antagonist radiotracer. Relative to LY-2795050, LY-2459989 displays 4-fold higher affinity for the KOR and similar selectivity and also possesses greatly improved central nervous system permeation. The drug appears to possess a short duration of action, with only 25% remaining in serum at 30 minutes post-injection in rhesus monkeys, making it an ideal agent for application in biomedical imaging, for instance in positron emission tomography.
Earlier analogues of LY-2459989 besides LY-2795050 with similar actions and potential uses have also been described.
