ABSTRACT
Human receptors have been shown to be clearly associated with a multitude of human diseases and disorders. Thus, these receptors have become molecular targets for drug discovery. There are several different structurally related superfamilies of human receptors including G-protein coupled receptors, cytokine receptors, receptor protein tyrosine kinases, ligand-gated ion channels, and steroid receptors and members from all of these superfamilies have been targeted in drug discovery programs. Screening for agonists and/or antagonists of various receptors has traditionally been accomplished by using radioligand binding assays. These assays are relatively simple to perform and are based upon the principles of a competitive binding assay in which the radiolabeled ligand competes with the unlabeled ligand for binding to a receptor in a cell or on the cell surface membrane. Thus, compounds or natural product extracts are evaluated for their ability to compete with a known ligand and this competition is measured by a decrease in the binding of the labeled known ligand. The focus of this section is to describe important aspects of developing and validating receptor radioligand binding assays used to screen combinatorial chemistry reaction products and natural product extracts.
