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Concept
Lead compound
Résumé
A lead compound (ˈliːd, i.e. a "leading" compound, not to be confused with various compounds of the metallic element lead) in drug discovery is a chemical compound that has pharmacological or biological activity likely to be therapeutically useful, but may nevertheless have suboptimal structure that requires modification to fit better to the target; lead drugs offer the prospect of being followed by back-up compounds. Its chemical structure serves as a starting point for chemical modifications in order to improve potency, selectivity, or pharmacokinetic parameters. Furthermore, newly invented pharmacologically active moieties may have poor druglikeness and may require chemical modification to become drug-like enough to be tested biologically or clinically.
Lead compounds are sometimes called developmental candidates. This is because the discovery and selection of lead compounds occurs prior to preclinical and clinical development of the candidate.
Before lead compounds can be discovered, a suitable target for rational drug design must be selected on the basis of biological plausibility or identified through screening potential lead compounds against multiple targets. Drug libraries are often tested by high-throughput screenings (active compounds are designated as "hits") which can screen compounds for their ability to inhibit (antagonist) or stimulate (agonist) a receptor of interest as well as determine their selectivity for them.
A lead compound may arise from a variety of different sources. Lead compounds are found by characterizing natural products, employing combinatorial chemistry, or by molecular modeling as in rational drug design. Chemicals identified as hits through high-throughput screening may also become lead compounds. Once a lead compound is selected it must undergo lead optimization, which involves making the compound more "drug-like." This is where Lipinski's rule of five comes into play, sometimes also referred to as the "Pfizer rule" or simply as the "rule of five.
Source officielle
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Proximité ontologique
Concepts associés (12)
Reverse pharmacology
In the field of drug discovery, reverse pharmacology also known as target-based drug discovery (TDD), a hypothesis is first made that modulation of the activity of a specific protein target thought to be disease modifying will have beneficial therapeutic effects. Screening of chemical libraries of small molecules is then used to identify compounds that bind with high affinity to the target. The hits from these screens are then used as starting points for drug discovery.
Hit to lead
Hit to lead (H2L) also known as lead generation is a stage in early drug discovery where small molecule hits from a high throughput screen (HTS) are evaluated and undergo limited optimization to identify promising lead compounds. These lead compounds undergo more extensive optimization in a subsequent step of drug discovery called lead optimization (LO).
Ethnomedicine
Ethnomedicine is a study or comparison of the traditional medicine based on bioactive compounds in plants and animals and practiced by various ethnic groups, especially those with little access to western medicines, e.g., indigenous peoples. The word ethnomedicine is sometimes used as a synonym for traditional medicine. Ethnomedical research is interdisciplinary; in its study of traditional medicines, it applies the methods of ethnobotany and medical anthropology. Often, the medicine traditions it studies are preserved only by oral tradition.