Lecture

Inhibitor Design & Analysis

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Description

This lecture covers the fundamentals of inhibitor design and analysis, focusing on the modes of action of reversible and irreversible drugs, developing chemical intuition for target engagement, and the importance of targeting cysteine residues. It also discusses the concepts of covalent vs. non-covalent parameters in successful drug development, with a special emphasis on the role of protein cysteines in drug resistance.

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Related concepts (32)

Enzyme inhibitor

An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a specific chemical reaction by binding the substrate to its active site, a specialized area on the enzyme that accelerates the most difficult step of the reaction.

Enzyme kinetics

Enzyme kinetics is the study of the rates of enzyme-catalysed chemical reactions. In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction are investigated. Studying an enzyme's kinetics in this way can reveal the catalytic mechanism of this enzyme, its role in metabolism, how its activity is controlled, and how a drug or a modifier (inhibitor or activator) might affect the rate. An enzyme (E) is typically a protein molecule that promotes a reaction of another molecule, its substrate (S).

Protease inhibitor (biology)

In biology and biochemistry, protease inhibitors, or antiproteases, are molecules that inhibit the function of proteases (enzymes that aid the breakdown of proteins). Many naturally occurring protease inhibitors are proteins. In medicine, protease inhibitor is often used interchangeably with alpha 1-antitrypsin (A1AT, which is abbreviated PI for this reason). A1AT is indeed the protease inhibitor most often involved in disease, namely in alpha-1 antitrypsin deficiency.

Cysteine protease

Cysteine proteases, also known as thiol proteases, are hydrolase enzymes that degrade proteins. These proteases share a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic triad or dyad. Discovered by Gopal Chunder Roy in 1873, the first cysteine protease to be isolated and characterized was papain, obtained from Carica papaya. Cysteine proteases are commonly encountered in fruits including the papaya, pineapple, fig and kiwifruit. The proportion of protease tends to be higher when the fruit is unripe.

Drug design

Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it.

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