JUQ‑097 – A Quick‑Start Guide to the Emerging Therapeutic Candidate Prepared for scientists, clinicians, and anyone with a professional interest in this novel molecule (as of April 2026).
1. What is JUJ‑097? | Item | Details | |------|----------| | Generic/Code name | JUQ‑097 (also referenced in some filings as JQ‑097 ). | | Developer | Janssen Pharmaceuticals (J&J) – the “JUQ” prefix follows Janssen’s internal naming convention for early‑stage CNS‑focused small‑molecule programs. | | Chemical class | Highly selective, non‑peptidic antagonist of the nociceptin/orphanin‑FQ peptide (NOP) receptor (also known as OPRL1 ). | | Molecular weight | ≈ 420 Da (exact value pending final publication). | | Formulation | Oral tablets (10 mg, 30 mg, 60 mg) for Phase II/III trials; a soluble‑capsule version is in pre‑clinical toxicology. | | Target indication(s) | Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD) with comorbid alcohol misuse . Secondary exploratory programs include opioid‑induced hyperalgesia and post‑traumatic stress disorder (PTSD). |
Bottom line: JUQ‑097 is the first selective NOP‑receptor antagonist to advance beyond Phase I, positioning itself as a potential disease‑modifying therapy for disorders where dysregulated nociceptin signaling contributes to stress‑related relapse and craving.
2. Why the NOP receptor? | Physiological role | Relevance to disease | |--------------------|----------------------| | Modulates stress‑induced reinstatement of drug‑seeking (rodent models). | Alcohol, opioids, and nicotine relapse are driven by NOP activation. | | Regulates dopamine release in the mesolimbic pathway . | Dampening NOP signaling restores normal reward processing, reducing craving. | | Interacts with the HPA‑axis (corticotropin‑releasing factor). | Chronic stress fuels depressive and anxiety phenotypes. | | Controls pain perception and analgesic tolerance . | Potential to counter opioid‑induced hyperalgesia. | In short, blocking NOP offers a dual‑action profile: anti‑craving + anti‑depressive/anti‑anxiolytic , a therapeutic niche not covered by current FDA‑approved medications for AUD (naltrexone, acamprosate, disulfiram). JUQ-097
3. Mechanism of Action (MoA)
Binding: JUQ‑097 binds to the orthosteric pocket of the NOP receptor with a Ki ≈ 0.8 nM, displaying > 100‑fold selectivity versus μ‑, κ‑, and δ‑opioid receptors. Antagonism: It prevents endogenous nociceptin (N/OFQ) from activating the receptor, thereby:
Reducing cAMP inhibition → normalizing neuronal excitability. Blocking β‑arrestin recruitment → limiting receptor desensitization. JUQ‑097 – A Quick‑Start Guide to the Emerging
Down‑stream effects:
Ventromedial prefrontal cortex (vmPFC) : Restores top‑down control over reward circuits. Nucleus accumbens (NAc) : Normalizes dopamine turnover, curbing “wanting” signals. Amygdala/HPA‑axis : Lowers cortisol surge in response to stress cues.
Pre‑clinical electrophysiology (slice recordings) shows that a single 30 mg dose reduces NOP‑mediated IPSCs by ~85 % in the central amygdala, with no measurable effect on MOR‑mediated currents. | Item | Details | |------|----------| | Generic/Code
4. Pre‑clinical Portfolio | Model | Key Findings | Translational Insight | |-------|--------------|-----------------------| | Alcohol‑preferring (P‑rats) | 60 % reduction in lever‑pressing for ethanol after 7 days of 30 mg/kg PO dosing. | Suggests robust anti‑craving effect. | | Stress‑induced reinstatement (mouse) | Blocked cue‑ and stress‑triggered reinstatement of cocaine seeking (p < 0.001). | Supports broader addiction applicability. | | Forced‑swim test (FST) | Dose‑dependent reduction in immobility time (≈ 30 % at 10 mg/kg). | Indicative of antidepressant‑like activity. | | Chronic pain (SNI model) | Prevented development of opioid‑induced hyperalgesia when co‑administered with morphine. | Potential adjunct for opioid stewardship. | | Safety/Tox | No QTc prolongation; NOAEL = 150 mg/kg/day (rat) with clean hepatic panel. | Favorable safety margin for human dosing. | Pharmacokinetics (rat):
t½ ≈ 8 h (oral), F ≈ 55 %, Cmax reached at 1.5 h, low brain‑to‑plasma ratio (0.6) – sufficient to achieve functional receptor occupancy (> 80 % at 30 mg). Minimal CYP450 inhibition (< 10 % of 3A4, 2D6, 2C9).