레타트루타이드 3상 임상 결과와 분자 구조 탐색의 새로운 방법

Medical Xpress recently reported that two Phase 3 clinical trials led by Northwestern University involving over 1,000 participants each have shown that the experimental weight-loss drug retatrutide can reduce body weight in patients with osteoarthritis (OA) of the knee by an average of 25% and significantly improve pain. Retatrutide is a triple agonist that simultaneously acts on the glucagon receptor (GCGR), GLP-1 receptor (GLP-1R), and GIP receptor (GIPR).

While the clinical impact of this 25% weight reduction is emphasized, the structural and molecular aspects of retatrutide's mechanism of action are often overlooked. Triple agonists, such as retatrutide, work by selectively binding to three different Class B GPCR subtypes (GCGR, GLP-1R, and GIPR), which share a common dimeric 7-transmembrane domain architecture but differ in their pocket environments, peptide sequence preferences, and allosteric coupling networks.

Traditional 2D structural representations fail to capture the nuances of these differences, making it challenging to visualize and compare the binding pockets of these three receptors simultaneously. To address this limitation, NexoPeek, a VR-based molecular visualization and analysis tool developed by Seven Sportz, allows users to interact with and compare the three receptor structures in 3D space.

NexoPeek enables users to load molecular files, switch between different visualization styles (cartoon, ball-and-stick, spacefill CPK, surface, B-factor heat map, and tubetrace), and perform various tasks such as pocket interaction analysis, foldseek structural alignment, hydrogen bond inspection, trigger-pick distance measurement, and residue highlighting.

These features provide a more intuitive understanding of retatrutide's unique triple agonist design and its effects on the binding pockets of the three GPCRs, ultimately contributing to the drug's clinical success in treating OA-related pain and weight management.