Radioligand Binding Assays

Pharmacological analysis in the simplest form for receptors, ion channels, and transporters is determination of the affinity of a drug for a target and this is determined by performing in vitro radioligand-binding assays. These assays are designed to measure the ability of a drug to compete with a radiolabeled compound that is selective for a particular target. Concentration-response curves are constructed and activity quantified as IC50 the molar concentration of drug that inhibits the binding...

The Drive to Miniaturize

The sharp rise in the number of compounds available for screening in the libraries of major pharmaceutical companies caused by combinatorial and automated chemistry efforts has driven both the increase in throughput of HTS and the attendant need for assay formats of lower volume and higher density. With typical pharmaceutical company compound libraries today being in the neighborhood of 106 compounds,63 high-density, low-volume formats are essential to prevent overlong screening campaigns,...

Benefit to Drug Discovery and Development

A major benefit of pharmacological profiling is the potential influence on decision-making in drug discovery. If key decisions can be made earlier in discovery, this avoids complications during the later, more resource intensive and expensive phases of drug development. One example of decision-making at early stages is where multiple chemical series are being evaluated and the primary pharmacology and physicochemical properties of the compounds make it difficult to distinguish between one...

Target Validation

Even if potent and selective chemical structures exist for a molecular target, the target is not validated for therapeutic intervention until efficacy can be demonstrated in clinical trials. Both the compound and the target are only fully validated for a disease when a drug is registered for the marketplace, which reflects the adequate safety or therapeutic index for a specified patient population by a specific route and frequency of dosing. For example, impairment of cholinergic pathways in...

Therapeutic Area

For life-threatening indications such as oncology, many participants felt that there is more willingness in clinical practice to stratify on the basis of pharmacogenetics and pharma-cogenomics. In other therapeutic areas in which many effective agents are already available and physicians are accustomed to titrating the dose in individual patients e.g., depression , it was thought that there was less willingness to stratify on the basis of phar-macogenetics and pharmacogenomics until differences...