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 (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 electr ...

or a

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

) 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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s and

nucleic acid Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...

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

pharmacologically active In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on organism, living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingred ...

compound Compound may refer to: Architecture and built environments * Compound (enclosure), a cluster of buildings having a shared purpose, usually inside a fence or wall ** Compound (fortification), a version of the above fortified with defensive struc ...

, the receptor target of a

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...

(like

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

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

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

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 the flow of io ...

s, and

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

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 In chemistry, a non-covalent interaction differs from a covalent bond in that it does not involve the sharing of electrons, but rather involves more dispersed variations of electromagnetic interactions between molecules or within a molecule. The ...

– 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 covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atoms ...

– 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 Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...

substances (such as activating hormones) from binding to the target. Depending on the nature of the target, this effect is referred as

receptor antagonism A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rec ...

enzyme inhibition An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a sp ...

, 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 A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

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 Therapeutic effect refers to the response(s) after a treatment of any kind, the results of which are judged to be useful or favorable. This is true whether the result was expected, unexpected, or even an unintended consequence. An adverse 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 compl ...

. 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 receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

s (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 fu ...

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

esterase An esterase is a hydrolase enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis. A wide range of different esterases exist that differ in their substrate specificity, their protein structure ...

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 Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...

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 the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, ...

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 receptors work with other proteins to regulate the expression of speci ...

s **

structural protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respond ...

s 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 cytoske ...

membrane transport protein A membrane transport protein (or simply transporter) 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 transmembran ...

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 In the field of drug discovery, reverse pharmacology also known as target-based drug discovery (TDD), a hypothesis is first made that modulation of the activity of a specific protein target thought to be disease modifying will have beneficial t ...

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) *

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. ...

* 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 or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

in human contraceptives, 17-R-ethinylestradiol, has been shown to increase the

feminization Feminization most commonly refers to: * Feminization (biology), the hormonally induced development of female sexual characteristics * Feminization (activity), a sexual or lifestyle practice where a person assumes a female role * Feminization (soci ...

of fish downstream from sewage treatment plants, thereby unbalancing reproduction and creating an additional

selective pressure Any cause that reduces or increases reproductive success in a portion of a population potentially exerts evolutionary pressure, selective pressure or selection pressure, driving natural selection. It is a quantitative description of the amount of ...

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