Active transport, Address-message concept, ADME, Affinity, Agonist, Allosteric binding sites, Allosteric enzyme, Allosteric regulation, Analog, Antagonist, Antimetabolite, Antisense molecule, Autacoid, Autoreceptor, Bioassay, Bioisostere, Bioprecursor prodrug, Biotransformation, CADD See Computer-assisted drug design., Carrier-linked prodrug (Carrier prodrug), Cascade prodrug, Catabolism, Catabolite , Clone, Codon, Coenzyme, Combinatorial library, Combinatorial synthesis, CoMFA See Comparative Molecular Field Analysis, Comparative Molecular Field Analysis (CoMFA), Computational chemistry, Computer-assisted drug design (CADD), Congener, Cooperativity, 3D-QSAR See Three-dimensional Quantitative Structure-Activity Relationship, De novo design, Disposition See Drug disposition, Distomer, Docking studies, Double-blind study, Double prodrug (or pro-prodrug), Drug, Drug disposition, Drug latentiation, Drug targeting, Dual action drug, Efficacy, Elimination, Enzyme, Enzyme induction, Enzyme repression, Eudismic ratio, Eutomer, Genome, Hansch analysis, Hapten, Hard drug, Heteroreceptor, Homologue, Hormone, Hydrophilicity, Hydrophobicity.
Active transport is the carriage of a solute across a biological membrane from low to high concentration that requires the expenditure of (metabolic) energy.
Address-message concept refers to compounds in which part of the molecule is required for binding (address) and part for the biological action (message).
Abbreviation for Absorption, Distribution, Metabolism, Excretion. (See also Pharmacokinetics; Drug disposition).
Affinity is the tendency of a molecule to associate with another. The affinity of a drug is its ability to bind to its biological target (receptor, enzyme, transport system, etc.) For pharmacological receptors it can be thought of as the frequency with which the drug, when brought into the proximity of a receptor by diffusion, will reside at a position of minimum free energy within the force field of that receptor.
For an agonist (or for an antagonist) the numerical representation of affinity is the reciprocal of the equilibrium dissociation constant of the ligand-receptor complex denoted
An agonist is an endogenous substance or a drug that can interact with a receptor and initiate a physiological or a pharmacological response characteristic of that receptor (contraction, relaxation, secretion, enzyme activation, etc.).
Allosteric binding sites
Allosteric binding sites are contained in many enzymes and receptors. As a consequence of the binding to Allosteric binding sites, the interaction with the normal ligand may be either enhanced or reduced.
An allosteric enzyme is an enzyme that contains a region to which small, regulatory molecules ("effectors") may bind in addition to and separate from the substrate binding site and thereby affect the catalytic activity.
On binding the effector, the catalytic activity of the enzyme towards the substrate may be enhanced, in which case the effector is an activator, or reduced, in which case it is a de-activator or inhibitor.
Allosteric regulation is the regulation of the activity of allosteric enzymes. (See also Allosteric binding sites; Allosteric enzymes).
An analog is a drug whose structure is related to that of another drug but whose chemical and biological properties may be quite different. (See also Congener).
An antagonist is a drug or a compound that opposes the physiological effects of another. At the receptor level, it is a chemical entity that opposes the receptor-associated responses normally induced by another bioactive agent.
An antimetabolite is a structural analog of an intermediate (substrate or coenzyme) in a physiologically occurring metabolic pathway that acts by replacing the natural substrate thus blocking or diverting the biosynthesis of physiologically important substances.
An antisense molecule is an oligonucleotide or analog thereof that is complementary to a segment of RNA (ribonucleic acid) or DNA (deoxyribonucleic acid) and that binds to it and inhibits its normal function.
An autacoid is a biological substance secreted by various cells whose physiological activity is restricted to the vicinity of its release; it is often referred to as local hormone.
An autoreceptor, present at a nerve ending, is a receptor that regulates, via positive or negative feedback processes, the synthesis and/or release of its own physiological ligand. (See also Heteroreceptor).
A bioassay is a procedure for determining the concentration, purity, and/or biological activity of a substance (e.g., vitamin, hormone, plant growth factor, antibiotic, enzyme) by measuring its effect on an organism, tissue, cell, enzyme or receptor preparation compared to a standard preparation.
A bioisostere is a compound resulting from the exchange of an atom or of a group of atoms with another, broadly similar, atom or group of atoms. The objective of a bioisosteric replacement is to create a new compound with similar biological properties to the parent compound. The bioisosteric replacement may be physicochemically or topologically based. (See also Isostere)
A bioprecursor prodrug is a prodrug that does not imply the linkage to a carrier group, but results from a molecular modification of the active principle itself. This modification generates a new compound, able to be transformed metabolically or chemically, the resulting compound being the active principle.
Biotransformation is the chemical conversion of substances by living organisms or enzyme preparations.
See Computer-assisted drug design.
Carrier-linked prodrug (Carrier prodrug)
A carrier-linked prodrug is a prodrug that contains a temporary linkage of a given active substance with a transient carrier group that produces improved physicochemical or pharmacokinetic properties and that can be easily removed in vivo, usually by a hydrolytic cleavage.
A cascade prodrug is a prodrug for which the cleavage of the carrier group becomes effective only after unmasking an activating group.
Catabolism consists of reactions involving endogenous organic substrates to provide chemically available energy (e.g., ATP) and/or to generate metabolic intermediates used in subsequent anabolic reactions.
A catabolite is a naturally occurring metabolite.
A clone is a population of genetically identical cells produced from a common ancestor. Sometimes, "clone" is also used for a number of recombinant DNA (deoxyribonucleic acid) molecules all carrying the same inserted sequence.
A codon is the sequence of three consecutive nucleotides that occurs in mRNA which directs the incorporation of a specific amino acid into a protein or represents the starting or termination signals of protein synthesis.
A coenzyme is a dissociable, low-molecular weight, non-proteinaceous organic compound (often nucleotide) participating in enzymatic reactions as acceptor or donor of chemical groups or electrons.
Combinatorial synthesis is a process to prepare large sets of organic compounds by combining sets of building blocks.
A combinatorial library is a set of compounds prepared by combinatorial synthesis.
See Comparative Molecular Field Analysis.
Comparative Molecular Field Analysis (CoMFA)**
Comparative molecular field analysis (CoMFA) is a 3D-QSAR method that uses statistical correlation techniques for the analysis of the quantitative relationship between the biological activity of a set of compounds with a specified alignment, and their three-dimensional electronic and steric properties. Other properties such as hydrophobicity and hydrogen bonding can also be incorporated into the analysis. (See also Three-dimensional Quantitative Structure-Activity Relationship [3D-QSAR]).
Computational chemistry is a discipline using mathematical methods for the calculation of molecular properties or for the simulation of molecular behaviour.
Computer-assisted drug design (CADD)**
Computer-assisted drug design involves all computer-assisted techniques used to discover, design and optimize biologically active compounds with a putative use as drugs.
A congener is a substance literally con- (with) generated or synthesized by essentially the same synthetic chemical reactions and the same procedures. Analogs are substances that are analogous in some respect to the prototype agent in chemical structure.
Clearly congeners may be analogs or vice versa but not necessarily. The term congener, while most often a synonym for homologue, has become somewhat more diffuse in meaning so that the terms congener and analog are frequently used interchangeably in the literature.
Cooperativity is the interaction process by which binding of a ligand to one site on a macromolecule (enzyme, receptor, etc.) influences binding at a second site, e.g. between the substrate binding sites of an allosteric enzyme. Cooperative enzymes typically display a sigmoid (S-shaped) plot of the reaction rate against substrate concentration. (See also Allosteric binding sites).
See Three-dimensional Quantitative Structure-Activity Relationship.
De novo design**
De novo design is the design of bioactive compounds by incremental construction of a ligand model within a model of the receptor or enzyme active site, the structure of which is known from X-ray or nuclear magnetic resonance (NMR) data.
See Drug disposition.
A distomer is the enantiomer of a chiral compound that is the less potent for a particular action. This definition does not excude the possibility of other effect or side effect of the distomer (See also Eutomer).
Docking studies are molecular modeling studies aiming at finding a proper fit between a ligand and its binding site.
A double-blind study is a clinical study of potential and marketed drugs, where neither the investigators nor the subjects know which subjects will be treated with the active principle and which ones will receive a placebo.
Double prodrug (or pro-prodrug)
A double prodrug is a biologically inactive molecule which is transformed in vivo in two steps (enzymatically and/or chemically) to the active species.
A drug is any substance presented for treating, curing or preventing disease in human beings or in animals. A drug may also be used for making a medical diagnosis or for restoring, correcting, or modifying physiological functions (e.g., the contraceptive pill).
Drug disposition refers to all processes involved in the absorption, distribution metabolism and excretion of drugs in a living organism.
Drug latentiation is the chemical modification of a biologically active compound to form a new compound, which in vivo will liberate the parent compound. Drug latentiation is synonymous with prodrug design.
Drug targeting is a strategy aiming at the delivery of a compound to a particular tissue of the body.
Dual action drug
A dual action drug is a compound which combines two desired different pharmacological actions at a similarly efficacious dose.
Efficacy describes the relative intensity with which agonists vary in the response they produce even when they occupy the same number of receptors and with the same affinity. Efficacy is not synonymous to Intrinsic activity.
Efficacy is the property that enables drugs to produce responses. It is convenient to differentiate the properties of drugs into two groups, those which cause them to associate with the receptors (affinity) and those that produce stimulus (Efficacy). This term is often used to characterize the level of maximal responses induced by agonists. In fact, not all agonists of a receptor are capable of inducing identical levels of maximal responses. Maximal response depends on the efficiency of receptor coupling, i.e., from the cascade of events, which, from the binding of the drug to the receptor, leads to the observed biological effect.
Elimination is the process achieving the reduction of of the concentration of a xenobiotic including its metabolism.
An enzyme is a macromolecule, usually a protein, that functions as a (bio) catalyst by increasing the reaction rate.
In general, an enzyme catalyzes only one reaction type (reaction selectivity) and operates on only one type of substrate (substrate selectivity). Substrate molecules are transformed at the same site (regioselectivity) and only one or preferentially one of chiral a substrate or of a racemate is transformed (enantioselectivity[special form of stereoselectivity]).
Enzyme induction is the process whereby an (inducible) enzyme is synthesized in response to a specific inducer molecule. The inducer molecule (often a substrate that needs the catalytic activity of the inducible enzyme for its metabolism) combines with a repressor and thereby prevents the blocking of an operator by the repressor leading to the translation of the gene for the enzyme.
Enzyme repression is the mode by which the synthesis of an enzyme is prevented by repressor molecules.
In many cases, the end product of a synthesis chain (e.g., an amino acid) acts as a feed-back corepressor by combining with an intracellular aporepressor protein, so that this complex is able to block the function of an operator. As a result, the whole operation is prevented from being transcribed into mRNA, and the expression of all enzymes necessary for the synthesis of the end product enzyme is abolished.
Eudismic ratio is the potency of the eutomer relative to that of the distomer.
The Eutomer is the enantiomer of a chiral compound that is the more potent for a particular action (See also Distomer).
A genome is the complete set of chromosomal and extrachromosomal genes of an organism, a cell, an organelle or a virus; the complete DNA (deoxyribonucleic acid) component of an organism.
Hansch analysis is the investigation of the quantitative relationship between the biological activity of a series of compounds and their physicochemical substituent or global parameters representing hydrophobic, electronic, steric and other effects using multiple regression correlation methodology.
A hapten is a low molecular weight molecule that contains an antigenic determinant but which is not itself antigenic unless combined with an antigenic carrier.
A hard drug is a nonmetabolizable compound, characterized either by high lipid solubility and accumulation in adipose tissues and organelles, or by high water solubility.
In the lay press the term "Hard Drug" refers to a powerful drug of abuse such as cocaine or heroin.
A heteroreceptor is a receptor regulating the synthesis and/or the release of mediators other than its own ligand (See also Autoreceptor).
The term homologue is used to describe a compound belonging to a series of compounds differing from each other by a repeating unit, such as a methylene group, a peptide residue, etc.
A hormone is a substance produced by endocrine glands, released in very low concentration into the bloodstream, and which exerts regulatory effects on specific organs or tissues distant from the site of secretion.
Hydrophilicity is the tendency of a molecule to be solvated by water.
Hydrophobicity is the association of non-polar groups or molecules in an aqueous environment which arises from the tendency of water to exclude non polar molecules. (See also Lipophilicity).
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