In pharmacology, an antitarget (or off-target) is a receptor, enzyme, or other biological target that, when affected by a drug, causes undesirable side-effects.
[1][2] Among the best-known and most significant antitargets are the hERG channel and the 5-HT2B receptor, both of which cause long-term problems with heart function that can prove fatal (long QT syndrome and cardiac fibrosis, respectively), in a small but unpredictable proportion of users.
Both of these targets were discovered as a result of high levels of distinctive side-effects during the marketing of certain medicines, and, while some older drugs with significant hERG activity are still used with caution, most drugs that have been found to be strong 5-HT2B agonists were withdrawn from the market, and any new compound will almost always be discontinued from further development if initial screening shows high affinity for these targets.
[9] According to David E. Nichols, "Discussions over the years with many colleagues working in the pharmaceutical industry have informed me that if upon screening a potential new drug is found to have serotonin 5-HT2A agonist activity, it nearly always signals the end to any further development of that molecule.
[10][11][12] The growth of the field of chemoproteomics has offered a variety of strategies to identify off-targets on a proteome wide scale.