Antitarget
Encyclopedia
In pharmacology
, an antitarget is a receptor
, enzyme
, or other biological target
that, when affected by a drug, causes undesirable side-effect
s. During drug design
and development
, it is important for pharmaceutical companies to ensure that new drugs do not show significant activity at any of a range of antitargets, most of which having been discovered largely through chance.
Among the best-known and most significant antitargets are the hERG
channel and the 5-HT2B receptor
, both of which causing 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hERG activity are still used with caution, most drugs that have been found to be strong 5-HT2B agonists were withdrawn from the market, and any new compound will almost always be discontinued from further development if initial screening shows high affinity for these targets.
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
, an antitarget is a receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
, enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
, or other biological target
Biological target
A biological target is a biopolymer such as a protein or nucleic acid whose activity can be modified by an external stimulus. The definition is context-dependent and can refer to the biological target of a pharmacologically active drug compound, or the receptor target of a hormone . The...
that, when affected by a drug, causes undesirable side-effect
Adverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
s. During drug design
Drug design
Drug design, also sometimes referred to as rational drug design or structure-based drug design, is the inventive process of finding new medications based on the knowledge of the biological target...
and development
Drug development
Drug development is a blanket term used to define the process of bringing a new drug to the market once a lead compound has been identified through the process of drug discovery...
, it is important for pharmaceutical companies to ensure that new drugs do not show significant activity at any of a range of antitargets, most of which having been discovered largely through chance.
Among the best-known and most significant antitargets are the hERG
HERG
hERG is a gene that codes for a protein known as Kv11.1 potassium ion channel...
channel and the 5-HT2B receptor
5-HT2B receptor
5-hydroxytryptamine receptor 2B, also known as HTR2B, is a 5-HT2 receptor, but also denotes the human gene encoding it.-Function:...
, both of which causing long-term problems with heart function that can prove fatal (long QT syndrome
Long QT syndrome
The long QT syndrome is a rare inborn heart condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsade de pointes . These episodes may lead to palpitations, fainting and sudden death due to ventricular fibrillation...
and cardiac fibrosis
Cardiac fibrosis
Cardiac fibrosis refers to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts.Fibrocyte cells normally secrete collagen, and function to provide structural support for the heart...
, 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.