A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Absorption The process of taking in, as when a sponge takes up water. Chemicals can be absorbed through the skin into the bloodstream and then transported to other organs. Chemicals can also be absorbed into the bloodstream after breathing or swallowing.
ADME Abbreviation for Absorption, Distribution, Metabolism, Excretion.
Affinity 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 anantagonist) the numerical representation of affinity is the reciprocal of the equilibrium dissociation constant of the ligand-receptor complex denoted KA, calculated as the rate constant for offset (k-1) divided by the rate constant for onset (k1).
Agonist A molecule that makes it easier for a post-synapatic cell to be influenced by neurotransmitters.
Amino acids Molecules containing amine (NH2) and carboxylic acid (COOH) which form the building blocks of proteins.
Analog A drug whose structure is related to that of another drug but whose chemical and biological properties may be quite different.
Antagonist A molecule that blocks the ability of a given chemical to bind to its receptor, preventing a biological response.
Assay A biological test, measurement or analysis to determine whether compounds have the desired effect either in a living organism, outside an organism, or in an artificial environment.
top
Biased libraries Libraries of compounds (putative drug leads) that exclude compounds unlikely to interact with particular protein family structures; these libraries are, therefore, "informed" by structure data. Broader term combinatorial libraries.
Bioassay Determination of the relative strength of a drug by comparing its effect on a test organism with that of a standard preparation.
Bioavailability The percentage of drug that is detected in the systemic circulation after its administration. Losses can be attributed to an inherent lack of absorption/passage into the systemic circulation and/or to metabolic clearance. Detection of drug can be accomplished pharmacodynamically (quantification of a biological response to the drug) or pharmacokinetically (quantification of actual drug concentration). Oral bioavailability is associated with orally administered drugs.
Bioisostere 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.
Biotechnology The industrial application of living organisms and/or biological techniques developed through basic research. Biotechnology products include pharmaceutical compounds and research materials.
Biotransformation The chemical conversion of substances by living organisms or enzymes preparations.
top
Chemical analysis The use of a standard chemical analytical procedures to determine the concentration of a specific analyte in a sample, or qualitatively or quantitatively measure a specific parameter of a sample.
Chemoinformatics The use of computer software to assist in the acquisition, analysis and management of data and information relating to chemical compounds and their properties.
Codrug A chemical structure that undergoes conversion to two or more active drugs within a biological system, such conversion usually involving metabolism. The term Twin Drug has previously been used to represent a codrug that specifically delivers two distinct and active agents, while the term Prodrug has been reserved for the delivery of a single active agent.
Combinatorial chemistry Technologies designed to greatly accelerate the rate at which potential new drugs are produced. Using robots and other advanced techniques, hundreds or thousands of different candidate compounds can be produced simultaneously.
Combinatorial library A set of compounds prepared by combinatorial chemistry. May consist of a collection of pools, or sub-libraries. Its composition may be described by the chemset notation. Narrower terms combinatorial peptide libraries, combinatorial protein libraries, compound library, hit optimization library, lead discovery library, biased libraries, combinatorial antibody libraries, directed libraries, focused libraries, pool, pool/ split libraries, sub-library, random libraries, unbiased libraries; Broader term: library.
Combinatorial organic synthesis A key feature of combinatorial techniques is that compound synthesis can be designed such that a range of structures can be produced simultaneously as mixtures in the same reaction vessel or individually in parallel using semi- automated synthesis. The repetitive nature of the synthetic processes involved in most combinatorial applications lends itself to automation or semi- automation. This key feature means that the bench chemist can single- handedly prepare tens, hundreds, or thousands of compounds of known structures in the time that it would take to prepare only a few pure entities by orthodox methodology.
Combinatorial synthesis A process to prepare large sets of organic compounds by combining sets of building blocks.
Computational chemistry A discipline using mathematical methods for the calculation of molecular properties or for the simulation of molecular behavior. It also includes, e.g., synthesis planning, database searching, combinatorial library manipulation.
top
De novo design 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.
Directed library (also biased- or focused library) Library which uses a limited number of building blocks chosen on the basis of pre-existing information or hypothesis which defines the type of functionalities deemed important to obtain a particular activity. For example, every member of the diketopiperazine library shown below contains the thiol pharmacophore known to interact with metalloproteinase enzymes.
Distillation The process of heating a liquid to its boiling point, removing the vapors through a cooling and condensing apparatus, and finally collecting the condensed liquid in a separate receiver. It is commonly used for the separation of two or more liquids in a mixture, or for the separation of the solvent from dissolved substances.
Diversity Some measure of the unrelatedness of a set of, for example, building blocks or members of a combinatorial library.
Docking studies Computational techniques for the exploration of the possible binding modes of a substrate [or ligand] to a given receptor, enzyme, or other binding site.
Drug 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.
Drug development process:
- Discovery: Identification of a biological, genetic or protein target linked to a particular disease; subsequent lead identification of a potential drug that interacts with the target to help cure the disease or halt its progression.
- Pre-clinical Phase: Comprehensive in vitro and animal testing of the drug candidate to establish its target specificity, toxicity in various doses and pharmacokinetics.
- Clinical Phase I: Human trials conducted to demonstrate safety and effectiveness (efficacy); tests with paid, healthy volunteers to establish dosage, side effects and pharmacokinetics.
- Clinical Phase II: Trials with small numbers of patients conducted to identify drug performance characteristics (optimal dosing, administration, key indication).
- Clinical Phase III: Pivotal trials conducted with larger patient populations to establish efficacy and provide additional safety information.
- Approval: Data is analyzed and submitted for regulatory review. The U.S. submission to the FDA is called an NDA (New Drug Application) or BLA (Biologic License Application); the European submission to the EMEA (European Medicines Evaluation Agency) is called an MAA (Marketing Authorization Application). After stringent analysis and review of the submission, the regulatory agency provides final approval.
Drug targeting A strategy aiming at the delivery of a compound to a particular tissue of the body.
top
Enzyme 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 of a chiral substrate or of a racemate is transformed (enantioselectivity [special form of stereoselectivity]).
Hard drug 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 refers to a powerful drug of abuse such as cocaine or heroin.
Heterogeneous Materials are not uniform throughout.
High-throughput screening Process for rapid identification of active samples from combinatorial library or other compound collection (generally 10s to 100s of thousands of compounds), typically by running parallel assays in plates of 96 or more.
Hit Library component with good level of desired activity.
Homogeneous Materials are the same throughout. All solutions are homogeneous.
Hydrogen bond A special situation that exists between the hydrogen atom in one molecule (like water) and the oxygen atom in another molecule (like another water molecule). This bond is ten times weaker than the covalent bond, and ten times stronger than the van der waals force. The hydrogen bond caused water to have its unusual properties of high boiling point, high melting point, high surface tension, and its formation of the six- sided ring structure in ice. The latter causes water to expand upon freezing, become less dense, and float in water.
top
Inhibitors Agents that block or suppress the activity of enzymes such as proteases.
In vitro Literally, "in glass" meaning in the test tube.
In vivo Literally, "in life" meaning in a living cell or organism.
Ion channel An integral membrane protein that provides for the regulated transport of (a) specific ion(s) across a membrane.
Isosteres Molecules or ions of similar size containing the same number of atoms and valence electrons.
top
LC-NMR: Liquid Chromatography Nuclear Magnetic Resonance Nuclear Magnetic Resonance spectroscopy (NMR) is a powerful analytical tool that can provide unambiguous structural information for small molecules. NMR, however, generally requires relatively high purity samples. Complex mixtures can give distorted and overlapping resonances making identification difficult. Furthermore, NMR detection is a relatively insensitive technique requiring substantial quantities of a particular analyte. The coupling of conventional HPLC [High Performance Liquid Chromatography] and NMR allows for detection and structural analysis of analytes in complex samples and is becoming an important mainstay in industry.
Lead compound A compound that exhibits pharmacological properties which suggest its value as a starting point for drug development.
Lead discovery The process of identifying active new chemical entities, which by subsequent modification may be transformed into a clinically useful drug.
Lead generation The term applied to strategies developed to identify compounds which possess a desired but non-optimized biological activity.
Lead optimization The synthetic modification of a biologically active compound, to fulfill stereoelectronic, physicochemical, pharmacokinetic and toxicologic [requirements associated with] clinical usefulness.
Ligand A small molecule that binds specifically to a larger one; for example, a hormone is the ligand for its specific protein receptor.
Ligand design The design of ligands using structural information about the target to which they should bind, often by attempting to maximize the energy of the interaction.
Lipid A water-insoluble molecule which is soluble in nonpolar solvents such as ether. Divided into two classes: Saponifiable and nonsaponifiable.
Lipophilic Capable of combining with or dissolving in lipids.
Lipophilicity The affinity of a molecule or a moiety for a lipophilic environment. It is commonly measured by its distribution behavior in a biphasic system, either liquid-liquid (e.g., partition coefficient in 1-octanol/water) or solid/liquid (retention on reversed-phase high performance liquid chromatography (RP-HPLC) or thin-layer chromatography (TLC) system).
top
Macromolecule A molecule having a molecular weight in the range of a few thousand to many millions: proteins, nucleic acids and polysaccharides.
Mass spectrometer A spectroscopic device in which the masses of particles, ions, and isotopes are measured. It separates isotopes according to charge and mass.
Medicinal chemistry a chemistry-based discipline, also involving aspects of biological, medical and pharmaceutical sciences. It is concerned with the invention, discovery, design, identification and preparation of biologically active compounds, the study of their metabolism, the interpretation of their mode of action at the molecular level and the construction of structure-activity relatioships.
Micromolar A concentration representing one millionth of a mole.
Moieties Chemical compounds or functional groups or portions of those compounds.
Mole The amount of pure substance that contains the same number of elementary entities as there are atoms in exactly 12 grams of the isotope carbon-12.
Molecular descriptors At the root of all methods devised to study the (dis)similarity of compounds; to predict physicochemical properties; to identify compounds with desirable or "drug- like" properties; and to select activity- enriched sets of molecules from "virtual" libraries (i.e., from large numbers of synthetically feasible compounds) are descriptors used to characterize the molecules. These include various types of molecular fingerprints, 3D pharmacophores, physicochemical properties, electrotopological states and connectivity indices. Some represent 2D molecules; some handle 3D ones.
Molecular formula Shows the actual number of atoms in compound. Ex. C2H4.
Molecular mass The sum of the atomic masses of all the atoms in a molecule.
Molecular modeling A technique for the investigation of molecular structures and properties using computational chemistry and graphical visualization techniques in order to provide a plausible three-dimensional representation under a given set of circumstances.
Molecular (dis-)similarity A measure of structural relatedness between pairs of molecules, e.g., the so-called Carbo, Hodgkin or Tanimoto coefficient.
top
Nanomolar A concentration representing one billionth of a mole.
New chemical entity (NCE) A compound not previously described in the literature.
NMR: Nuclear Magnetic Resonance NMR spectroscopy makes it possible to discriminate nuclei, typically protons, in different chemical environments. The electron distribution gives rise to a chemical shift of the resonance frequency. The chemical shift of a nucleus is expressed in parts per million (ppm) by its frequency, n, relative to a standard, ref, and defined as = 106 (n - ref)/o, where o is the operating frequency of the spectrometer. It is an indication of the chemical state of the group containing the nucleus. More information is derived from the spin-spin couplings between nuclei, which give rise to multiplet patterns. Greater detail may be derived from two- or three- dimensional techniques. These use pulses of radiation at different nuclear frequencies, after which the response of the spin system is recorded as a free- induction decay (FID). Multidimensional techniques, such as COSY and NOESY, make it possible to deduce the structure of a relatively complex molecule such as a small protein (molecular weight up to 25,000). In proteins containing paramagnetic centres, nuclear hyperfine interactions can give rise to relatively large shifts of resonant frequencies known as contact and pseudo- contact (dipolar) shifts, and considerable increases in the nuclear spin relaxation rates. From this type of measurement, structural information can be obtained about the paramagnetic site. A technology for protein structure determination. NMR generally gives a lower-resolution structure than X-ray crystallography does, but it does not require crystallization. NMR is currently applicable only to smaller proteins.
Optimization The process of synthesizing chemical variations, or analogs, of a lead compound, with the goal of creating those compounds with improved pharmacological properties.
Oxidation In a broad sense oxidation is the increase in positive valence of any element in a substance. On the basis of the electron theory, oxidation is a process in which an element losses electrons. In a narrow sense, oxidation means the chemical addition of oxygen to a substance.
top
Parallel synthesis Strategy whereby sets of discrete compounds are prepared simultaneously in arrays of physically separate reaction vessels or microcompartments without interchange of intermediates during the assembly process.
Peptide A molecule composed of two or more amino acids. Larger peptides are generally referred to as polypeptides or proteins.
Peptide bond A planar, amide linkage between the ?-amino group of one amino acid and the ?-carboxyl group of another, with the elimination of a molecule of water.
Pharmacokinetics The study of absorption, distribution, matabolism and excretion (ADME) of bioactive compounds in a higher organism.
Pharmacology The science of studying both the mechanisms and the actions of drugs, usually in animal models of disease, to evaluate their potential therapeutic value.
Pharmacophore (pharmacophoric pattern) - A pharmacophore is the ensemble of steric and electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target structure and to trigger (or to block) its biological response. A pharmacophore does not represent a real molecule or a real association of functional groups, but a purely abstract concept that accounts for the common molecular interaction capacities of a group of compounds towards their target structure.
Potency Refers to the concentration of an agent (drug) at which it inhibits an enzyme to a defined extent, i.e. IC50 is the concentration at which an inhibitor blocks the activity of an enzyme 50 per cent.
Privileged structure Substructural feature which confers desirable (often drug- like) properties on compounds containing that feature. Often consists of a semi- rigid scaffold which is able to present multiple hydrophobic residues without undergoing hydrophobic collapse.
Prodrug A chemical structure that undergoes conversion to an active drug within a biological system, such conversion usually involving metabolism.
Protease An enzyme that hydrolyzes (breaks down a bond and adds water) proteins, especially to peptides.
Protein A molecule composed of a long chain of amino acids. Proteins are the principal constituents of cellular material and serve as enzymes, hormones, structural elements, and antibodies. The molar mass is usually above 100,000.
Protein kinases Enzymes that phosphorylate certain amino acid residues (most often Ser, Thr, or Tyr) in specific proteins.
top
Quantitative analysis chemical determination of the amounts or proportions of constituents in a substance.
Quantitative Structure-Activity Relationships (QSAR) Mathematical relationships linking chemical structure and pharmacological activity in a quantitative manner for a series of compounds. Methods which can be used in QSAR include various regression and pattern recognition techniques.
Receptor A molecule within a cell or on a cell surface to which a substance (such as a hormone or a drug) selectively binds, causing a change in the activity of the cell.
Rules of five: Lipinski's rules Set of criteria for predicting the oral bioavailability of a compound on the basis of simple molecular features (molecular weight, CLogP, numbers of hydrogen- bond donors and acceptors). Often used to profile a library or virtual library with respect to the proportion of drug- like members which it contains. An algorithm, developed by Christopher A. Lipinski (of Pfizer) and colleagues, in which many of the cutoff numbers are five or multiples of five. There are actually four rules, and Pfizer has developed a additional number of criteria for adoption of lead candidates.
top
Salinity (1) the relative concentration of salts, usually sodium chloride, in a given water. It is usually expressed in terms of the number of ppm of chloride. (2) a measure of the concentration of dissolved mineral substances in water.
Scaffold Core portion of a molecule common to all members of a combinatorial library.
Serine protease A family of proteases, characterized by a serine amino acid at its active site.
Solid-fase synthesis Synthesis of compounds on a solid surface such as tiny plastic beads. In solid-phase approaches, pin or bead techniques permit the synthesis of different molecules on each pin (i.e., "one molecule- one bead"). The products of solid-phase synthesis can be cleaved from the backbone matrix for solution screening (which is essential when the screening target is a cell), or the most active molecules displayed on the polymer surface may be detected using molecular targets (receptor, enzyme, antibody) pre-tagged with a means of detection (visible color, fluorescence, radioactivity, chromophore, etc.) and then isolated and identified.
Solution phase Solution-phase combinatorial approaches have recently become of interest as an alternative drug discovery avenue for lead discovery and optimization. The key advantages of solution-phase combinatorial approaches include (1) an unlimited number of reactions can be used, therefore, providing maximal structural diversity, (2) an unlimited reaction scale allows for the generation of sufficient quantities of libraries to be derived into different diverse libraries and tested in a broad range of assays, (3) a large excess of reagents and solvents, typically required in solid-phase chemistry, are not needed in solution-phase chemistry, (4) there is no need for linker manipulation, attachment to and detachment from resin; therefore, the reaction sequences for library generation are shorter, (5) soluble intermediates and final products can be obtained directly for purification and assays, (6) it is easy to develop and monitor solution-phase reactions, and (7) it is an efficient way for lead discovery and optimization from single-compound and complex libraries.
Spectroscopy Is the analysis of the lines of light emitted from excited atoms as the electrons drop back through their orbitals. These lines give the energy and distances of the electronic orbitals.
Structure-Activity Relationship (SAR) An analysis which defines the relationship between the structure of a molecule and its ability to affect a biological system.
top
Template A macromolecular pattern for the synthesis of another molecule. For example, DNA is a template for RNA synthesis.
Thematic libraries synthesis Over the past several years, combinatorial chemistry has gradually realigned itself with changing business needs. In many organizations diversity-driven library production intended to broadly cover druglike chemical space has to a large extent been replaced by thematic as well as project-directed libraries. Thematic libraries are particularly useful for a platform target-based approach to drug discovery because the control of a common biochemical theme (e.g., the use of enzyme inhibitors, peptidomimetics of receptor ligands, etc.) can often cross over providing leads in several therapeutic areas.
Three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) The analysis of the quantitative relationship between the biological activity of a set of compounds and their spatial properties using statistical methods.
top
Unbiased library Library prepared from building blocks chosen without bias towards a particular target.
Van der Waals forces Weak interactions between molecules. (Note: chemical bonds are the forces between atoms in a molecule whereas van der waals forces are between molecules). These weak forces are caused by the attraction between protons in one molecule and electrons in an adjacent molecule. Because of the greater distance between the particles in one molecule and another, van der waals forces are only 1/100 as strong as the covalent bond.
Virtual library A library which exists solely in electronic form or on paper. The building blocks required for such a library may not exist, and the chemical steps for such a library may not have been tested. These libraries are used in the design and evaluation of possible libraries.
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
| 
