How Drugs Act: Concepts for Therapy

So far, only a relatively small fraction of the druggable genome has been the subject of pharmacological targeting. Enzymes are very popular drug targets, and protein kinases are a particularly promising target family. Enzymes do not bind to their substrates and reaction products in a particularly strong way. Instead, they bind the substrate in a geometry that prepares it for the transition state of the reaction. Sometimes only small structural changes are needed to convert a substrate into an inhibitor. Natural substrates are often the starting point for rational drug design. There are three types of enzyme inhibitors: competitive inhibitors, non-competitive inhibitors, and allosteric inhibitors. Enzyme inhibition can also be classified as reversible and irreversible. Reversible inhibition is desirable today, but some very important drugs are irreversible inhibitors, and some reversible inhibitors have such high affinities that they are effectively irreversible inhibitors. Receptors are also important drug targets. They can be divided into GPCRs, ion channels, hormone receptors, and growth factor receptors. An agonist activates the receptor, an antagonist prevents the agonist from docking to its binding site, and an inverse agonist stabilizes an inactive conformation of the receptor. Ion channels are extremely fast gateways for ions and can be either voltage- or ligand-gated. Ions can only passively flow through an ion channel within a concentration gradient. Transporters are specialized proteins in the membrane. They can pump molecules and ions against the concentration gradient at the expense of ATP hydrolysis. Many transporters are attractive drug targets, and others are responsible for the development of drug resistance. There is a wide variety of known modes of drug action. The goal in targeting these modes of action is to find a pathophysiological process that is unique to the disease. Drug resistance is an increasingly serious problem and is both an inevitable consequence of the use of pharmaceutical therapy and a consequence of its misuse, particularly in the case of anti-infectives. The question of combination therapy is controversial. Nevertheless, some drug combinations are justified and contribute to compliance, clinical efficacy and safety. https://sn.pub/01mfsx