Glossary

ABC transporters:	(ATP-Binding Cassette Transporters) A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein. Scientific nomenclature of ABC transporters in SOLVO membranes
Absorption:	In pharmacology absorption is the process that results in the transport or diffusion of the drug from the site of administration to the blood. More commonly, absorption is the process where orally administered drugs get into the blood through the intestinal epithelial cells.
ADME:	Absorption, Distribution, Metabolism and Excretion
ADMET:	ADME/toxicology. An ideal drug candidate must have an acceptable balance of potency, selectivity, pharmacokinetic properties and toxicity. Poor pharmacokinetics and toxicity of candidate compounds is a primary cause of costly late stage failures in drug development. It is imperative that these properties be considered as early as possible and integrated throughout drug discovery and development to enable early attrition of candidate compounds and prevent unnecessary expenditure of time and money. New assays and systems aimed at early ADME-Tox prediction are increasingly making their presence felt in drug discovery and development.
Aliquot:	(analytical chemistry) a known amount of a homogeneous material, assumed to be taken with negligible sampling error. The term is usually applied to fluids.
Animal model:	A laboratory animal useful for medical research because it has specific characteristics that resemble a human disease or disorder. Scientists can create animal models, usually laboratory mice, by transferring new genes into them.
Anthracyclines:	Anthracylines are a group of chemotherapy drugs used to treat a variety of cancers, mostly leukemias.
Antibody:	A component of the body's immune response. A Y-shaped protein, it is secreted in response to an antigenic stimulus. It neutralizes the antigen by binding to it, and facilitates clearance of antigen by various mechanisms.
Apical plasma membrane:	The term used for the cell membrane on the apical (inner or upper) surface of transporting epithelial cells. This region of the cell membrane is separated, in vertebrates, from the baso-lateral membrane by a ring of tight junctions that prevents free mixing of membrane proteins from these two domains.
Assay:	Analysis of a substance, or of components in a mixture, or of the biological, chemical, or pharmacological potency of a drug.
ATP:	ATP is a molecule which consists of the nitrogenous base adenine linked to the sugar ribose and which has a chain of three phosphate groups attached to the ribose in a linear fashion. ATP is present in all living cells and serves as an energy source for many metabolic processes; energy is released when ATP is hydrolyzed into ADP. It is the single most important molecule in all living things since it serves as the currency for energy in biological systems.
ATPase:	Enzyme that catalyzes a process involving the hydrolysis of ATP. A large number of different proteins, including ABC transporters, have ATPase activity.
Baculovirus vectors:	They are used for expression of foreign genes in insects.
Basolateral plasma membrane:	The plasma membrane of epithelial cells that is adjacent to the basal lamina or the adjoining cells of the sheet. Differs both in protein and phospholipid composition from the apical plasma membrane from which it is isolated by tight junctions.
Bicistronic vector:	A construct that expresses two proteins from a single messenger RNA.
Bile acids and salts:	Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.
Bile salt export pump protein:	Gene sister of P-glycoprotein is closely related to Pgp, it is involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Bile:	An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol ; and electrolytes. It aids digestion of fats in the duodenum.
Biliary canalicular membrane of hepatocytes:	Apical membrane of polarized hepatocytes forming the bile canaliculus.
Biotechnology:	The integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services.
Blood-brain barrier:	The BBB has several important functions as protects the brain from "foreign substances" in the blood that may injure the brain, protects from hormones and neurotransmitters in the rest of the body and also maintains a constant environment for the brain. It is semi-permeable; that is, it allows some materials to cross, but prevents others from crossing. In most parts of the body, the smallest blood vessels, called capillaries, are lined with endothelial cells. The endothelial tissue has small spaces between each individual cell so substances can move readily between the inside and the outside of the vessel. However, in the brain, the endothelial cells fit tightly together and substances cannot pass out of the bloodstream.
Brush border membrane of intestinal cells:	The densely packed microvilli on the apical surface of the intestinal epithelial cells (brush border cells). The microvilli aid absorption by increasing the surface area of the cells of the gut lumen.
Caco-2:	The Caco-2 cell line is an immortalized line of heterogenous human epithelial colorectal adenocarcinoma cells. Monolayers of Caco-2 cells are widely used to predict the absorption of compounds. This tool is also suitable to study active transport processes.
Calcein AM:	A non-fluorescent compound cleaved to a fluorescent compound by non-specific intracellular esterases.
Cancer:	A general term for about 100 diseases characterized by uncontrolled, abnormal growth of cells. The resulting mass, or tumor, can invade and destroy surrounding normal tissues. Cancer cells from the tumor can spread throughout the blood or lymph (the clear fluid that bathes body cells) to start new cancers in other parts of the body (metastases).
Carcinoma:	A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer".
cDNA:	Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Cell based assays:	The term is used to refer to any of a number of different experiments based on the use of live cells. This is a general definition and can include a variety of assays that measure cell proliferation, toxicity, motility, production of a measurable product, and morphology. Cell-based assays offer a more accurate representation of the real-life model since live cells are used, and also offer the possibility of a dynamic experiment through monitoring the numbers or behavior of the live cells. Thus, they provide a framework to determine the changes an external factor may exert on overall cellular function and viability.
Cell culture:	The in vitro propagation of animal of plant cells, in an artificial nutrient medium.
Cell line:	Established cell cultures that have the potential to propagate indefinitely.
Cell signaling:	Cell communication, any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.
Cell suspension:	Unattached floating cells in liquid culture medium.
Channel blocker:	Any drug that blocks membrane channel functions. More commonly any of a class of drugs, which prevents the calcium ions, needed for muscle contraction from entering the cells of smooth and cardiac muscle. This causes blood vessel walls to relax and blood to flow more freely to the heart, lowering blood pressure and relieving anginal pain.
Chemotherapy:	Any therapy using chemically synthesized drugs; more commonly, the application of such methods in the treatment of cancer.
Cholestasis:	Impairment of bile flow due to obstruction in small bile ducts (intrahepatic cholestasis) or obstruction in large bile ducts (extrahepatic cholestasis).
Cloning, Molecular	The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Custom made:	Made according to the specifications of an individual.
Cystic fibrosis:	An inherited disease of exocrine glands, affecting most characteristically the pancreas, respiratory system, and sweat glands, usually beginning in infancy and typified by chronic respiratory infections, pancreatic insufficiency, and susceptibility to heat prostration. Cirrhosis of liver occurring in childhood is common and may produce portal hypertension, splenomegaly, and hypersplenism.
Cytostatic:	Inhibiting or suppressing cellular growth and multiplication.
Deficiency syndrome:	Disease that arises due to the functional impairment of a protein most frequently as the consequence of the sequence alterations in the gene.
Digoxin:	It is a cardiac glycoside used in the treatment of different heart conditions. It is a substrate of the ABCB1 (MDR1, Pgp) transporter and is widely used probe to study the ABCB1 mediated active transport both in vitro and in vivo.
DMPK:	Drug metabolism and pharmacokinetics.
Drug interactions:	The action of a drug (termed perpetrator) that may affect the activity, metabolism, or toxicity of another drug (termed victim).
Drug toxicity:	Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques.
Drug:	Any substance which when absorbed into a living organism may modify one or more of its functions. The term is generally accepted for a substance taken for a therapeutic purpose, but is also commonly used for abused substances. Synonymous with medicine, pharmaceutical.
Dubin-Johnson syndrome:	An inherited disorder characterized by mild jaundice throughout life. Dubin-Johnson syndrome is inherited as an autosomal recessive disorder. The transport of bilirubin from the liver into the biliary system is abnormal and the bilirubin accumulates in the liver.
Efflux pump:	Proteins, located in the cell membrane, which transport molecules out of the cell.
Endogenous:	Produced inside an organism or cell.
Endothelial cell of the brain capillaries:	Monomolecular cell layer separating the blood and brain tissue. Play a major role in blocking xenobiotic and some endogenous substances from entering the brain.
Endothelial cells:	Highly specialized cells that line the endothelium. They are polygonal in shape and joined together by tight junctions. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.
Epithelial cells in the choroid plexus:	One of the barriers separating blood from the cerebrospinal fluid (CSF). Plays important role in blocking xenobiotic and some endogenous substances from entering the brain.
Epithelial cells:	Cells that line the inner and outer surfaces of the body.
Expression system:	In genetic engineering, the cells into which a gene has been inserted to manufacture desired proteins.
Expression:	Usually used to refer to the entire process of producing a protein from a gene, which includes transcription, translation, post-translational modification and possibly transport reactions.
Familial HDL deficiency:	High-density lipoprotein (HDL) protects against atherosclerosis by a reverse cholesterol transport that collects cholesterol from peripheral cells, including those in the arterial wall, for delivery to the liver and sterol-metabolizing organs. Familial HDL deficiency patients have low HDL levels and thus prone to atherosclerosis. Familial HDL deficiency is inherited in an autosomal dominant fashion.
Familial intrahepatic cholestasis:	(PFIC) is a severe type of cholestatic liver disease that is inherited as an autosomal recessive trait. This intrahepatic impairment of bile flow presents in infancy and results in liver failure.
Flow-cytometry:	An instrument that allows one to gather information from single cells by light scattering or fluorescence properties. These provide information on the size and internal complexity (forward scatter and side scatter, respectively) as well as "markers", identified by staining with fluorescent probes such as conjugated antibodies in the case of immunophenotyping, or nucleic acid dyes in the case of reticulocyte enumeration and DNA content analysis.
Fluorescent microplate reader:	An instrument that reads fluorescent signal, emitted from samples arranged in microplates. Microplates contain 96 wells or multiples of 96 wells.
Gene therapy:	The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia.
Granulocyte:	Leukocyte with conspicuous cytoplasmic granules. In humans the granulocytes are also classified as polymorphonuclear leucocytes and are subdivided according to the staining properties of the granules into eosinophils, basophils and neutrophils. Plays important role in antimicrobial defense and modulate allergic and inflammatory responses.
Hepatocyte:	The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.
HTS:	(High Throughput Screening) Process for rapid assessment of the activity of samples from a combinatorial library or other compound collection, often by running parallel assays in plates of 96 or more wells.
In vitro:	A biological or biochemical process carried out in a test-tube, culture plate or similar vessel.
In vivo:	A biological or biochemical process occurring in a living organism.
Intestinal cell:	Cells of intestine. More commonly, polarized intestinal epithelial cells, that the most important barrier to absorption of orally administered drugs.
Knockout mice:	Mice whose genome contains a gene whose function has been disrupted, or "knocked- out". A common method of producing disabled genes using recombinant DNA technology is by inserting an antibiotic resistance gene into the normal DNA sequence of a clone of the gene being studied. This disrupts the gene's action, thereby preventing it from making an active protein product. Cells in which this transfer is successful are then injected into mouse embryos, producing chimeric mice. These mice are bred to yield a strain in which all the cells contain the knocked- out gene. Knockout mice are used as animal models for various diseases, such as cystic fibrosis, and are helping to clarify the functions of the genes studied within the fields of immunology, cancer genetics, and developmental biology.
Knockout:	Inactivation of specific genes. Knockouts are often created in laboratory organisms such as yeast or mice so that scientists can study the knockout organism as a model for a particular disease.
Lead molecule:	A molecule showing expected efficacy in relevant in vitro pharmacological models, often also passed the preliminary in vitro toxicological and ADME screening, is ready to be taken into lead optimization.
Lead optimization:	The complex process of refining the chemical structure of a hit to improve its drug characteristics, with the goal of producing a pre-clinical drug candidate. The synthetic modification of a biologically active compound, to fulfill all stereoelectronic, physicochemical, pharmacokinetic and toxicologic required for clinical usefulness.
Lead:	A representative of a compound series with sufficient potential (as measured by potency, selectivity, pharmacokinetics, physicochemical properties, absence of toxicity and novelty) to progress to a full drug development programme.
Leishmania:	Parasitic flagellated protozoans which cause diseases in animals including humans, most notably leishmaniasis.
Lipid disorders:	Lipid disorders are abnormalities in the amount of fatty substances, called lipids, in the blood. Cholesterol and triglycerides are two types of lipids measured. These lipids are involved in many body processes.
Liquid scintillation:	It is a method for measuring radiation from beta-emitting nuclides. It is widely used to quantify ³H- and ¹⁴C-labeled compounds.
Luminal membrane in the proximal tubulus of the kidney:	Apical membrane of tubular columnar epithelial cells. Site of reabsorption of various endogenous molecules and secretion (efflux) of some endogenous and xenobiotic substances.
MDR modulator:	Any compound that modifies multi-drug resistance.
MDR protein:	Multi-drug resistance protein, a type of ABC transporter protein that can pump hydrophobic drugs (such as some anti-cancer drugs) out of the cytoplasm of eucaryotic cells.
Membrane transport proteins:	Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport, facilitated transport and ion channels.
Microdialysis:	It is a technique used to determine the chemical components of the fluid in the extracellular space of tissues. It is widely used to measure the concentration of compounds in the central nervous system.
MRP:	Multi-drug resistance protein.
Multidrug resistance:	Resistance of tumors or infectious agents to a wide-range of therapeutic compounds. In cancer multidrug resistance ABC-MDR proteins actively expel the cytotoxic drugs from cells, maintaining the drug level below a cell-killing threshold. Drug extrusion mediated by these primary active transporters is driven by the energy of ATP hydrolysis. The most intriguing characteristic distinguishing the ABC-MDR proteins from other mammalian transporters is their wide substrate specificity. Unlike other selective (classical) transport proteins, multidrug transporters recognize and handle a wide range of substrates. This wide substrate specificity explains the cross-resistance to several chemically unrelated compounds, the characteristic feature found in the multidrug resistance phenotype.
Mutagenesis:	A natural or intentional/research-oriented alteration of the coding region of genes, yielding modified proteins.
Neurogenic inflammation:	Inflammation caused by an injurious stimulus of peripheral neurons and resulting in release of neuropeptides which affect vascular permeability and help initiate proinflammatory and immune reactions at the site of injury.
Orthotopic tumor models:	Transplanted tumors that grow at the normal site (e.g. hepatocellular carcinoma cells forming a tumor in the liver).
PAMPA:	Short for "Parallel Artificial Membrane Permeation Assay", a technique used to measure the passive permeability of compounds across a hydrophobic layer. It is used to predict passive, transcellular permeability of compounds.
PCR technology:	Polymerase chain reaction (PCR) is a rapid, inexpensive and simple method for producing relatively large numbers of copies of DNA molecules from minute quantities of source DNA material--even when the source DNA is of relatively poor quality. It has rapidly become one of the most widely used techniques in molecular biology and molecular pathology.
Permeability:	Ability of a compound to passively diffuse across biological membranes.
P-gp/P-glycoprotein:	A protein which pumps alien chemicals, including certain anti-cancer drugs, out of living cells.
P-gp-inhibitor:	A compound that acts as an MDR modulator by the inhibition of P-gp.
Pharmacokinetic:	The study of absorption, distribution, metabolism and excretion of a drug.
Phenotype:	The outward appearance of the individual. It is the product of interactions between genes, and between the genotype and the environment.
Pluripotent:	Able to generate numerous cell types.
Predictive ADME:	Computational (in silico) screening has become a valuable tool to predict the interaction of a compound with the biological system. Absorption, Distribution, Metabolism, Excretion and Toxicology are all important issues to consider when developing accurate and predictive models.
Progenitor cells:	Ancestor cells that can restore function in tissues damaged by disease. Progenitor cells found in the bone marrow, for instance, are stimulated by the recombinant protein erythropoietin to form mature red blood cells.
Protease inhibitors:	Compounds which inhibit or antagonize biosynthesis or actions of proteases.
Protein kinases:	A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Pseudoxanthoma elasticum:	(PXE) A rare disorder of degeneration of the elastic fibres with tiny areas of calcification in the skin, back of the eyes (retinae), and blood vessels. Pseudoxanthoma elasticum is inherited from the parents, either as an autosomal recessive or as an autosomal dominant trait. It typically causes yellow-white small raised areas in the skin folds, often appearing in the second or third decades of life. These skin abnormalities frequently appear on the neck, armpits, and other areas that bend a great deal (referred to as flexure areas). The face is not affected. There are often see abnormalities in the retina called angioid streaks, which are tiny breaks in the elastin-filled tissue there. These eye abnormalities can lead to blindness. Other areas that can be affected in pxe include the heart which can be affected by atherosclerosis and mitral valve prolapse. Small blood vessels are abnormally fragile in patients with pxe because the blood vessel walls contain elastin and are weakened. This can lead to abnormal bleeding in such areas as the bowel and, very rarely, the uterus. Impairment of circulation to the legs can lead to pains in the legs while walking (claudication).
R&D:	research and development
Recombinant:	A new combination of genes that forms DNA. Recombinant DNA technology allows for the production of wild type and modified human proteins at large quantities.
Rheumatoid Arthritis:	Rheumatism of the joints, which could be any of a variety of disorders marked by inflammation, degeneration, or metabolic derangement of the connective tissue structures of the body.
Sandwich cultured hepatocytes:	Hepatocytes cultured between two layers of collagen (in a collagen "sandwich") acquire growth and protein expression characteristics that are very similar to the in vivo situation. This makes this tool suitable to predict the interaction of compounds with liver enzymes and transporters.
Screening:	Pharmacological or toxicological screening consists of a specified set of procedures to which a series of compounds is subjected to characterize pharmacological and toxicological properties and to establish dose- effect and dose- response relationships.
Selectable marker:	Gene that allows for selection of cells carrying the gene. More commonly, selectable markers provide resistance against cytotoxic insults.
Sf9:	An insect ovarian cell, Spodoptera frugiperda (Sf9), has been widely used to express recombinant proteins, as a host cell in the baculovirus expression system.
Solid tissue neoplasms:	Neoplasms growing in solid tissue (vs. haematological neoplasms that grow in blood or blood-forming tissue).
Solid tumor:	Cancer of body tissues other than blood, bone marrow, or the lymphatic system.
Spectrophotometry:	Employed to measure the amount of light that a sample absorbs.
Stargardt disease:	Also known as fundus flavimaculatus is the most common form of inherited juvenile macular degeneration. It is characterized by a reduction of central vision with a preservation of peripheral (side) vision.
Stem cells:	Stem cells are relatively undifferentiated cells that can develop into different/any kind of cell in the human body. Most cells have a specific function eg. liver cells, skin cells, brain cells and so forth and once they have taken on this function, in a process called differentiation, they can't be adapted for any other function. Stem cells, however, have not gone through the differentiation process.
Substrate:	In biochemistry, a substrate is a molecule undergoing a reaction, for which the presence of an enzyme lowers the activation energy. The substrate binds with the enzyme's active site, and the enzyme provides an alternative reaction pathway with a lower activation enthalpy.
Tangier disease:	Genetic disorder of cholesterol transport is caused by mutations in the ABC1 (ATP-binding cassette) gene on chromosome 9q31. ABC1 codes for a protein that helps rid cells of excess cholesterol. This cholesterol is then picked up by HDL particles in the blood and carried to the liver, which processes the cholesterol to be reused in cells throughout the body. Individuals with Tangier disease are unable to eliminate cholesterol from cells, leading to its buildup in the tonsils and other organs.
Target:	Molecules in the body that may be addressed by drugs to produce a therapeutic effect.
Teratology:	The branch of embryology and pathology that deals with abnormal development and congenital malformations.
Transduction, genetic:	The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a gene transfer technique.
Transgenic:	An experimentally produced organism in which DNA has been artificially introduced and incorporated into the organism's germ line, usually by injecting the foreign DNA into the nucleus of a fertilized embryo.
Vesicle:	A relatively small and enclosed compartment, separated from the cytosol by at least one lipid bilayer. Vesicles store, transport, or digest cellular products and wastes.
Vesicular transport:	This is a method of transport that does not require any movement of proteins across membranes. Instead, proteins are packaged in vesicles which bud off from one compartment and fuse with the membrane of an other.
Xenobiotic:	Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.