GPCR Drug Discovery In Vitro Assays
G protein-coupled receptors (GPCRs), also known as seven transmembrane domain receptors, 7TM receptors, or G protein-linked receptors (GPLR), are cell surface receptors that detect chemicals outside the cell and induce physiological responses. GPCRs are the most intensively studied drug targets. Scientists reveals 475 medicines (~34% of all FDA-approved drugs) target 108 different GPCRs. There are currently 321 medicines in clinical trials, with 20% of them targeting 66 potentially unique GPCR targets that have yet to be discovered and treated.
To advance the success of your projects, Creative Biolabs offers a wide range of GPCR in vitro assays to evaluate the therapeutic effects of your candidate against the membrane protein targets.
Category of GPCR Drug Discovery In Vitro Assays
Structure and Classification
Although the precise number of the GPCR superfamily is unknown, genome sequence analysis has projected that they are encoded by at least 831 distinct human genes, or about 4% of the overall protein-coding genome. GPCRs are classified into six classes based on sequence and function: Class A-rhodopsin-like receptors, Class B-secretin receptors, Class C-metabotropic glutamate receptors, Class D-fungal mating pheromone receptors, Class E-cAMP receptors, and Class F-frizzled and smoothened receptors. Class A is by far the largest class, accounting for 85% of GPCR genes. Olfactory receptors are predicted to make up more than half of class A GPCRs, with the other receptors either being orphan receptors or being liganded by known endogenous substances. GPCRs are made up of seven transmembrane (7TM) that are connected by three extracellular (ECL) loops and three intracellular (ICL) loops.
Signaling Pathway
The main sequence and tertiary structure of the GPCR itself place restrictions on the signaling pathways that can be triggered by it, but the final decision is made by the conformation that a given ligand stabilizes as well as the accessibility of transducer molecules. G-proteins and β-arrestins are currently thought to be the two main types of transducers used by GPCRs. The majority of signaling ultimately depends on G-protein activation because β-arr's have high affinity only for the phosphorylated version of the majority of GPCRs. G proteins are made up of two functional units: an α subunit (Gα) and a βγ complex (Gβγ). For heterotrimeric G proteins, agonist-activated GPCRs operate as guanyl nucleotide exchange factors. The nucleotide-binding pocket of the receptor-bound G protein opens, allowing GDP to leave the inactive form and be replaced by GTP, which is much more abundant in the cytoplasm. After the GTP-bound G protein-subunit dissociates from the receptor, both G protein subunits bind to their respective effectors. At this level, a freed active receptor can bind and activate another G protein molecule, causing in signal amplification.
