HMN 2026: What is the 30 years of adhesion GPCR modulators and their key concentrations

Adhesion GPCRs are a large class of surface proteins that recognize chemical and mechanical stimuli in the body. The rapidly expanding body of knowledge on the therapeutic targeting of these receptors is raising hopes for clinical application in the near future. Although no medicinal products targeting these receptors have yet been approved, several adhesion GPCR modulators are available and show potential for translation into clinical use. Modulators are crucial for the regulation of metabolic pathways and play a major role in pharmacology by enabling the targeted control of receptor activity.

A new study provides a comprehensive compilation of all known natural and synthetic therapeutic modulators of adhesion GPCRs, evaluates how they work, and presents key data on effective concentrations in clearly structured tables. It also offers an overview of the physiological functions of this receptor family identified to date. The scholarly article condenses 30 years of research on adhesion GPCRs into nearly 300 references, tracing the path from molecules with previously unknown functions to tangible therapeutic strategies.

The information is intended to serve as practical guidance for researchers, clinicians and representatives of the pharmaceutical industry. “Knowledge about the role of adhesion GPCRs in human disease is expanding rapidly. With our work, we aim to help further strengthen the bridge between basic research and clinical application,” says Professor Ines Liebscher, study lead at the Rudolf Schönheimer Institute of Biochemistry, part of the Faculty of Medicine.

Researchers at the institute are currently developing new compounds designed to target individual signaling pathways of these receptors. Particular attention is being paid to what are called biased agonists—active substances that selectively stimulate specific signaling cascades and may therefore minimize unwanted side effects. In addition to their influence on metabolic processes, diseases of the cardiovascular system, myelination disorders and cancer development are also a focus of research.

Researchers at Leipzig University and Shandong University only recently jointly discovered the active compound AP503, a highly specific activator of the adhesion GPCR GPR133. In various mouse models, AP503 was shown to improve muscle contractility and to mitigate bone loss associated with osteoporosis. The article published in Nature Reviews Drug Discovery marks the fourth successful collaboration between the Rudolf Schönheimer Institute of Biochemistry and the team led by Professor Jin-Peng Sun at Shandong University.

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