GPCRs in Drug Discovery and Safety Pharmacology
G protein coupled receptors (GPCRs) have been and will continue to be prominent drug targets for treating hypertension, pain, asthma, neurological and other disorders. There are ~385 druggable GPCRs, which can share similar binding pockets. Because one drug may interact with more than one receptor, profiling a drug candidate’s GPCR activity can reveal off-target effects, which can be either good or bad for drug safety and efficacy.
Why Profile GPCRs with Functional Assays vs. Binding Assays?
Unlike ligand-binding assays, high-quality, cell-based, functional assays,
such as those developed and validated by Merck, can truly elucidate the effect of a compound on GPCR signaling.
- Functional data can reveal potential safety liability at an off-target hit
- Functional assays and binding assays are equally sensitive assays for antagonists
- Functional assays are more sensitive for detecting agonists and off-target interactions
- Limited radioligands and quality membrane preps means fewer targets can be profiled by binding assays
Easily explore the human GPCRome