Novel Chemical Probe for Cannabinoid Receptor Subtype 2 (CB2): XIE35 and Its Analogs

University of Pittsburgh researchers have identified a novel chemical probe, XIE35, for the cannabinoid receptor subtype 2 (CB2). This compound exhibits high selectivity and nanomolar binding affinity to CB2, making it a valuable tool for cannabinoid drug research. XIE35 and its analogs have potential applications as anti-inflammatory agents and fluorescence dye compounds for fluorometric binding assays. This discovery opens new avenues for developing CB2-targeted therapies without psychotropic side effects.

Fig presents two graphs of radiometric binding assay studies, showing that the compound of Formula II has high CB2 binding affinity, CB2 (31.7 nM) (A), but weak CB1 binding affinity, CB1(4185 nM) (B).

Description

The compound XIE35 is a newly identified chemical probe with high biological activity that binds selectively to the CB2 receptor. Using a combination of NMR conformations, pharmacophore models, 3D pharmacophore database queries, and biovalidation, researchers have established the proof of concept for CB2 biological selectivity. XIE35 has a unique chemical scaffold and demonstrates potent CB2 binding affinity (Ki = 31.7 nM) while showing weak affinity for the CB1 receptor (Ki = 4185 nM). This compound can be further modified to develop a novel class of potent CB2 ligands.

Applications

• Cannabinoid drug research
• Anti-inflammatory agent
• Fluorescence dye for fluorometric binding assays
• Immune therapy targeting CB2 receptor

Advantages

XIE35 offers a novel chemical scaffold with high CB2-specific biological binding affinity, providing a specific chemical probe for cannabinoid research and drug discovery. The compound's high selectivity for CB2 over CB1 reduces the risk of psychotropic side effects, making it a promising candidate for therapeutic applications. Additionally, its potential use as a fluorescence dye enhances its utility in binding assays and screening novel cannabinoid ligands.

Invention Readiness

The invention is at the preclinical stage, with proof of concept for CB2 biological selectivity established. XIE35 was identified through 3D pharmacophore database searches and validated using radiometric binding assays. Further cell-based functional studies are ongoing to evaluate the compound's therapeutic potential, including its effects on G-protein signaling and anti-inflammatory properties.

IP Status

https://patents.google.com/patent/WO2009058377A1