A biological target is anything within a living organism to which some other entity (like an endogenous

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

or a

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets are

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s and

nucleic acid Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a pentose, 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nuclei ...

s. The definition is context-dependent, and can refer to the biological target of a pharmacologically active

compound, the receptor target of a

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

(like

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

), or some other target of an external stimulus. Biological targets are most commonly proteins such as

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

s, and receptors.

Mechanism

The external stimulus (''i.e.'', the drug or ligand) physically binds to ("hits") the biological target. The interaction between the substance and the target may be: * noncovalent – A relatively weak interaction between the stimulus and the target where no chemical bond is formed between the two interacting partners and hence the interaction is completely reversible. * reversible covalent – A chemical reaction occurs between the stimulus and target in which the stimulus becomes chemically bonded to the target, but the reverse reaction also readily occurs in which the bond can be broken. * irreversible covalent – The stimulus is permanently bound to the target through irreversible chemical bond formation. Depending on the nature of the stimulus, the following can occur: * There is no direct change in the biological target, but the binding of the substance prevents other endogenous substances (such as activating hormones) from binding to the target. Depending on the nature of the target, this effect is referred as receptor antagonism, enzyme inhibition, or ion channel blockade. * A conformational change in the target is induced by the stimulus which results in a change in target function. This change in function can mimic the effect of the endogenous substance in which case the effect is referred to as receptor agonism (or channel or enzyme activation) or be the opposite of the endogenous substance which in the case of receptors is referred to as inverse agonism.

Drug targets

The term "biological target" is frequently used in pharmaceutical research to describe the native protein in the body whose activity is modified by a drug resulting in a specific effect, which may be a desirable therapeutic effect or an unwanted

adverse effect An adverse effect is an undesired harmful 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. The term compli ...

. In this context, the biological target is often referred to as a drug target. The most common drug targets of currently marketed drugs include: * proteins ** G protein-coupled receptors (target of 50% of drugs) **

s (especially

protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them ( phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a f ...

s, proteases,

esterase In biochemistry, an esterase is a class of enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis (and as such, it is a type of hydrolase). A wide range of different esterases exist that differ ...

s, and

phosphatase In biochemistry, a phosphatase is an enzyme that uses water to cleave a phosphoric acid Ester, monoester into a phosphate ion and an Alcohol (chemistry), alcohol. Because a phosphatase enzyme catalysis, catalyzes the hydrolysis of its Substrate ...

s) ** ion channels ***

ligand-gated ion channel Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as sodium, Na+, potassium, K+, calcium, Ca2+, and/or chloride, Cl− to ...

s ***

voltage-gated ion channel Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in a Cell (biology), cell's electrical membrane potential near the channel. The membrane potential alters the conformation of t ...

s **

nuclear hormone receptor In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These intracellular receptors work with other proteins to regulate the exp ...

s ** structural proteins such as

tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytosk ...

membrane transport protein A membrane transport protein is a membrane protein involved in the movement of ions, small molecules, and macromolecules, such as another protein, across a biological membrane. Transport proteins are integral membrane proteins, integral transmembr ...

s * nucleic acids

Drug target identification

Identifying the biological origin of a disease, and the potential targets for intervention, is the first step in the discovery of a medicine using the reverse pharmacology approach. Potential drug targets are not necessarily disease causing but must by definition be disease modifying. An alternative means of identifying new drug targets is forward pharmacology based on phenotypic screening to identify "orphan" ligands whose targets are subsequently identified through target deconvolution.

Databases

Databases containing biological targets information: * Therapeutic Targets Database (TTD)
DrugMap
*

DrugBank The DrugBank database is a comprehensive, freely accessible, online database containing information on drugs and drug targets created and maintained by the University of Alberta and The Metabolomics Innovation Centre located in Alberta, Canada. A ...

* Binding DB

Conservation ecology

These biological targets are conserved across species, making pharmaceutical pollution of the environment a danger to species who possess the same targets. For example, the synthetic

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

in human

contraceptives Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth control only be ...

, 17-R-ethinylestradiol, has been shown to increase the feminization of fish downstream from sewage treatment plants, thereby unbalancing reproduction and creating an additional selective pressure on fish survival. Pharmaceuticals are usually found at ng/L to low-μg/L concentrations in the aquatic environment. Adverse effects may occur in non-target species as a consequence of specific drug target interactions. Therefore, evolutionarily well-conserved drug targets are likely to be associated with an increased risk for non-targeted pharmacological effects.

References