For decades, GPCRs were paradoxical targets: biologically central, yet structurally elusive. These receptors mediate key signaling pathways involved in sensory processing, metabolism, immune function, and neurotransmission. We knew they mattered, but for a long time, many GPCRs were labeled โundruggableโ due to their dynamic conformations, membrane localization, and limited structural insight.
๐ช๐ต๐ฎ๐ ๐๐ต๐ถ๐ณ๐๐ฒ๐ฑ ๐๐ต๐ฒ ๐ณ๐ถ๐ฒ๐น๐ฑ?
– Breakthroughs in structural biology (cryo-EM and stabilized receptor constructs).
– Better understanding of biased signaling and allosteric modulation.
– Advances in computational modeling and high-throughput screening.
– A recognition that functional selectivity can be as important as affinity.
๐ง๐ต๐ฒ ๐ฟ๐ฒ๐๐๐น๐?
Today, GPCRs represent one of the most druggable and productive target classes in medicine, accounting for ~33% of approved drugs covering oncology, cardiology, neurology, metabolic disease and rare disorders.
๐ฆ๐ผ ๐๐ต๐ฎ๐โ๐ ๐ป๐ฒ๐
๐?
– Precision GPCR targeting.
– Biased agonists with improved safety profiles.
– Orphan GPCRs moving from biology to bona fide drug programs.
– Next-generation stabilized constructs.
The GPCR story is a powerful reminder that โundruggableโ is often just a temporary label, one that innovation, persistence and cross-disciplinary science can overturn.
๐๐๐ฟ๐ถ๐ผ๐๐ ๐๐ผ ๐ต๐ฒ๐ฎ๐ฟ
Which GPCR advances do you think will define the next decade of therapeutics?
Evolution of GPCR research
