Sunobinop TFA  (Synonyms: S 117957 TFA; IMB 115 TFA)

Sunobinop (S 117957) TFA is an orally active and blood-brain barrier-permeable selective partial agonist of the human nociceptin/orphanin FQ receptor (NOP), which exhibits high affinity for human targets (K_i=3.3 nM; EC₅₀=4.03 nM; E_max=47.8%) without activating μ and κ opioid receptors. Sunobinop TFA significantly reduces wakefulness time and increases non-rapid eye movement sleep in rats by activating NOP receptors, and produces no significant side effects on learning, memory, reward, respiration or intestinal function at effective doses. Sunobinop TFA displays competitive antagonist properties in specific signaling pathways, such as β-arrestin 2 recruitment. With these unique pharmacological properties, Sunobinop TFA can be used to investigate insomnia, moderate-to-severe alcohol use disorder, and urinary incontinence caused by overactive bladder^[1][2].

Sunobinop (1 pM-1 μM) TFA acts as a moderately potent partial agonist at human NOP receptors in calcium mobilization assays, and exhibits no activity at classical opioid receptors, demonstrating high selectivity for NOP receptors^[2].
Sunobinop (10 pM-10 μM; 1 h pre-incubation) TFA acts as a moderately potent partial agonist of human NOP receptors in cAMP inhibition assays, reducing forskolin-stimulated cAMP levels with a potency reaching approximately 72% of the maximal efficacy of N/OFQ^[2].
Sunobinop (10 pM-10 μM) TFA acts as a low-efficacy, moderately potent partial agonist in bioimpedance assays using HEK293 cells expressing the NOP receptor, and functions as a competitive antagonist when co-incubated with N/OFQ^[2].
Sunobinop TFA exhibits human pEC₅₀ values of 7.99, 7.62, 7.22, and 8.07 in various NOP assays^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Sunobinop (30-300 mg/kg; p.o.; single dose) TFA significantly reduces wakefulness and increases non-REM sleep in WT rats via NOP receptor activation, with no adverse effects on cognitive, reward, respiratory, or gastrointestinal function at supratherapeutic doses^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

549.58

C₂₈H₃₄F₃N₃O₅

Solid

White to off-white

O=C1N([C@@H]2C[C@H]3N([C@]4([H])C[C@@H]5C[C@@H](CCC5)C4)[C@H](CCC3)C2)C6=CC=CC=C6N=C1C(O)=O.O=C(O)C(F)(F)F

Room temperature in continental US; may vary elsewhere.

-20°C, stored under nitrogen, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)

• [1]. Whiteside GT, et al. The nociceptin/orphanin FQ receptor partial agonist sunobinop promotes non-REM sleep in rodents and patients with insomnia. J Clin Invest. 2024;134(1):e171172.  [Content Brief]

  [2]. Camilotto R, et al. In vitro pharmacological evaluation of the novel NOP receptor partial agonist sunobinop. Biochem Pharmacol. 2025;238:116972.  [Content Brief]