The 146th Annual Meeting of the Pharmaceutical Society of Japan (Osaka)

Organizer: Ryoji Suno (Kansai Med. Univ.), Tsuyoshi Saitoh (IIIS, Tsukuba Univ.)

G protein-coupled receptors (GPCRs) govern diverse physiology and remain targets for ~30% of approved drugs. SBDD has been effective, but structure determination long posed a bottleneck. Recent cryo-electron microscopy (cryo-EM) now enables rapid, high-resolution structures across active and inactive states. In parallel, advances in pharmacology, molecular dynamics (MD), and AI-driven construct design and prediction are clarifying biased signaling and subtype selectivity. Integrating dynamic and static information is starting to support more rational GPCR drug discovery. Meanwhile, many orphan GPCRs, whose endogenous ligands remain unknown, persist; defining their physiological roles is key to expanding the target landscape. A practical cycle - functional elucidation -> structure determination -> ligand design -> functional validation - lets orphan GPCR research and SBDD drive each other, opening paths to once-intractable areas. This symposium will present recent technologies and implementations, including cryo-EM, pharmacological profiling, MD, and AI-assisted design, and discuss how their integration defines "GPCR Pharmacology 2.0" and opens new fronts for next-gen therapeutics.