June 2022
"G protein-coupled receptors (GPCRs) represent a major therapeutic target class as they play a key role in many (patho-) physiological processes. GPCRs are divided into six classes based on amino acid sequence similarities, but only four of the classes (A, B, C, and F) are found in humans. GPCRs respond to a wide variety of signals that range in size from photons to proteins (Foord et al., 2005). GPCRs continue to be regarded as one of the most tractable classes of drug targets and are targeted by 30%–40% of current drugs (Hauser et al., 2017), with annual sales of GPCR-targeting drugs in 2018 accounting for >114 billion USD. In 2019, 5 out of 20 first-in-class approved therapeutic agents targeted GPCRs. Despite this high number of GPCR targeted drugs, only a small portion (∼110) of the human GPCRome (consisting of approximately 850 GPCRs) has been successfully drugged, and obtaining highly potent and selective small molecules remains a challenge for the remainder."