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 ele ...

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 inhal ...

) 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, respon ...

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 ...

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 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 metabol ...

), 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 substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

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 ...

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 An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agoni ...

(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 ...

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 Pharmaceutical drug, medication or other Surgery#Definitions, intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main ...

. 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 form ...

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 monoester into a phosphate ion and an alcohol. Because a phosphatase enzyme catalyzes the hydrolysis of its substrate, it is a subcategory of hydrolases. Ph ...

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 re ...

s *** voltage-gated ion channels ** nuclear hormone receptors ** structural proteins such as tubulin **

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 membrane prote ...

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 Therapeutic Target Database (TTD) is a pharmaceutical and medical repository constructed by the Innovative Drug Research and Bioinformatics Group (IDRB) at Zhejiang University, China and the Bioinformatics and Drug Design Group at the Nation ...

(TTD) * DrugBank * 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 a ...

in human contraceptives, 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 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