Antitarget
An antitarget is an enzyme , a receptor , an ion channel or another biomolecule to which an active ingredient should not bind or activate. When binding or activating an antitarget by an active substance, undesirable effects are to be expected. The antitarget is thus the opposite of a target , the target structure of an active ingredient. Antitargets play a role especially in drug research. Already in the early phases of drug development, substances that could potentially bind to antitargets are identified and sorted out with the help of bio- and cheminformatics and later with the help of pharmacological methods.
Examples
Well-known examples of antitargets are the hERG channel , the 5-HT 2B receptor and the cytochrome P450 isoenzymes . Activation of the hERG channel, a potassium channel , has been associated with cardiac arrhythmias . Numerous drugs that caused cardiac arrhythmia due to hERG channel activation, such as astemizole , cisapride , clobutinol , grepafloxacin , sertindole , terfenadine or thioridazine , have been withdrawn from the market or their use has been severely restricted. Activation of the 5-HT 2B receptor was seen as the cause of the increased occurrence of heart valve damage and pulmonary hypertension after taking the appetite suppressants fenfluramine and dexfenfluramine as well as benfluorex and led to their withdrawal from the market.
While the hERG channel and the 5-HT 2B receptor are pharmacodynamic antitargets, the cytochrome P450 isoenzymes can be classified as pharmacokinetic antitargets. Inhibition of these isoenzymes can lead to numerous drug interactions .
Individual evidence
- ↑ Klaus Klebe: Binding undesirable: hERG potassium channel as an antitarget . In: drug design . Springer DE, 2009, ISBN 3827422132 , pp. 338-340.
literature
- Roy J. Vaz, Thomas Klabunde: Methods and Principles in Medicinal Chemistry , Volume 77: Antitargets. John Wiley & Sons, 2008, ISBN 3527621474 .