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JTC-801 free base is a small molecule, orally active, selective antagonist of the nociceptin receptor (also known as opioid receptor-like1 or ORL1). It was developed as an analgesic agent and has been evaluated for its use in cancer treatment and pain management, including neuropathic, cancer-related, and postoperative pain. The compound blocks the nociceptin receptor with high affinity (Ki ~8.2 nM), thereby modulating pain signaling pathways distinct from classical opioid receptors. While it also weakly inhibits δ-, κ-, and μ-opioid receptors at higher concentrations, its primary mechanism is antagonism of the nociceptin receptor. Clinical development reached phase II trials but was discontinued[1][3][5][7].
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