Seltorexant (JNJ-42847922) Research Standard

Seltorexant (JNJ-42847922, MIN-202) is a potent, orally active, and highly selective Orexin-2 Receptor (OX2R) antagonist. By selectively modulating the orexin signaling pathway, which is integral to arousal and the regulation of the sleep–wake cycle, Seltorexant has emerged as a significant reference compound in neurobiological and pharmacological research. In laboratory and analytical settings, it is utilized to probe the kinetics of the Orexin-2 receptor, map receptor-ligand binding interactions, and investigate the physiological implications of OX2R antagonism in experimental models.

Technical Specifications

Mechanism of Action & Research Context

Seltorexant is engineered for high-affinity binding to the Orexin-2 receptor. Its structural features—including the specific fluorine atom positioning and the triazole ring system—are critical for its pharmacological profile.

• OX2R Selectivity: The compound exhibits high selectivity for the Orexin-2 receptor over the Orexin-1 receptor (OX1R). Researchers use this selectivity to isolate the effects of OX2R antagonism in cell-based assays and radioligand competition studies.

• Binding Pocket Interaction: The molecule’s three-dimensional shape enables a precise fit within the OX2R binding pocket. This makes it an ideal probe for studying receptor-ligand kinetics and displacement dynamics using labeled tracers.

• Signaling Modulation: By acting as an antagonist, Seltorexant inhibits the downstream signaling pathways associated with orexin-induced arousal, providing a mechanism to study the reduction of wake-promoting neurochemical activity in controlled in vitro models.

Research Applications

Seltorexant is a specialized reagent essential for modern neuropharmacology and receptor research.

Primary fields of in vitro and analytical laboratory investigation include:

• Binding Affinity Assays: Measuring K_i values and binding kinetics to establish potency and selectivity profiles against OX2R versus OX1R.

• Competition Binding Studies: Utilizing radioligand displacement assays to map the binding footprint within the Orexin-2 receptor.

• Protein Binding Analysis: Evaluating the free fraction of the compound in plasma solutions to support pharmacokinetic modeling.

• Receptor Mapping: Employing the compound as a structural probe to examine how specific ligand modifications influence receptor affinity.

Storage & Handling Guidelines

Store at controlled room temperature. Keep tightly closed. Liquid formats: do not refrigerate or freeze. Cold storage may cause the solution to cloud or precipitate. If this occurs, return to room temperature and mix until clear.

Storage guidance is a house recommendation. Analytical documentation is per-lot release testing.