 | |
| Clinical data | |
|---|---|
| Routes of administration | Oral,intravenous |
| ATC code |
|
| Pharmacokinetic data | |
| Eliminationhalf-life | 15 minutes (in rhesus monkeys)[1] |
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| UNII | |
| CompTox Dashboard(EPA) | |
| Chemical and physical data | |
| Formula | C23H22FN3O2 |
| Molar mass | 391.446 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
LY-2459989 is asilent antagonist of theκ-opioid receptor (KOR) that has been developed byEli Lilly as aradiotracer of thatreceptor, labeled either withcarbon-11[1] orfluorine-18.[2]
LY-2459989 exhibits greatly improvedcentral nervous system permeation relative to LY-2795050, with brain levels approximately six times higher than those of its predecessor.[1] The compound has a short duration of action, with only 25% of the compound remaining in serum 30 minutes post-injection inrhesus monkeys, making it an ideal agent for application inbiomedical imaging, such aspositron emission tomography (PET).[1]
LY-2459989 possesses highaffinity for the KOR (Ki = 0.18 nM) and is highly selective for it over theμ-opioid receptor (Ki = 7.68 nM) and theδ-opioid receptor (Ki = 91.3 nM), showing over 43-fold selectivity for the KOR relative to the otheropioid receptors.[1] LY-2459989 is afluorine-containinganalogue and follow-up compound ofLY-2795050, the first KOR-selective antagonist radiotracer.[1] Relative to LY-2795050, LY-2459989 displays 4-fold higher affinity for the KOR and similar selectivity.[1]
Earlier analogues of LY-2459989 besides LY-2795050 with similar actions and potential uses have also been described.[4] Short-acting κ antagonists of this type have been shown to produce antidepressant-like effects in animal studies.[5]
