Chemistry:LY-2459989
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| Routes of administration | Oral, intravenous |
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| Elimination half-life | 15 minutes (in rhesus monkeys)[1] |
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| Formula | C23H22FN3O2 |
| Molar mass | 391.446 g·mol−1 |
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LY-2459989 is a silent antagonist of the κ-opioid receptor (KOR) that has been developed by Eli Lilly as a radiotracer of the aforementioned receptor, labeled either with carbon-11[1] or fluorine-18.[2] It possesses high affinity for the KOR (Ki = 0.18 nM) and is highly selective for it over the μ-opioid receptor (Ki = 7.68 nM) and the δ-opioid receptor (Ki = 91.3 nM) (over 43-fold selectivity for the KOR over the other opioid receptors).[1] LY-2459989 is a fluorine-containing analogue and follow-up compound of LY-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 and also possesses greatly improved central nervous system permeation (brain levels were found to be 6-fold higher than those of LY-2795050).[1] 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 (PET).[1]
Earlier analogues of LY-2459989 besides LY-2795050 with similar actions and potential uses have also been described.[3]
See also
- κ-Opioid receptor § Antagonists
- List of investigational antidepressants
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "An Improved Antagonist Radiotracer for the κ-Opioid Receptor: Synthesis and Characterization of (11)C-LY2459989". J. Nucl. Med. 55 (7): 1185–91. 2014. doi:10.2967/jnumed.114.138701. PMID 24854795.
- ↑ "Fluorine-18-Labeled Antagonist for PET Imaging of Kappa Opioid Receptors". ACS Chem Neurosci 8 (1): 12–16. 2017. doi:10.1021/acschemneuro.6b00268. PMID 27741398.
- ↑ "Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer". J. Med. Chem. 54 (23): 8000–12. 2011. doi:10.1021/jm200789r. PMID 21958337.
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