ADME | Studies on the absorption, distribution, metabolisation and elimination of a drug. |
Agonist | Molecule which interacts with a specific receptor and activates observed biochemical and cellular events. An agonist is generally a molecule which has certain structural similarities with a physiological ligand which it may substitute. |
Amino acids | The building blocks of proteins or peptides. The molecules of amino acids are interlinked to form peptidic bonds. |
AMM | Administrative autorisation to commercialise a drug under specific conditions (therapeutic indication, patient profiles….) (Autorisation de Mise sur le Marché). |
Antagonist | Molecule which interacts with a specific receptor and which blocks the activation of biochemical and cellular events. An antagonist may be a molecule having certain structural similarities to a physiological ligand, and which is linked to the receptor by displacing the interaction between the receptor and its physiological ligand. |
Antibody | Complex immunoglobulin protein used by the immune system to detect and neutralise pathogenic agents such as bacteria and viruses. |
Arteriosclerosis | Generally, the term "sclerosis" indicates the fibrous degeneration of a tissue or of an organ. With age, tissues which constitute the arteries loose their elasticity and become more rigid. The normal aging of the arteries is called arteriosclerosis. Arteriosclerosis also affects smaller arteries and arterioles and is very often accompanied by lipid deposits in the internal wall of the arteries. |
Atheroma patches | The accumulation of deposits, made up of notably lipids, which are generally produced at the site of the bifurcation of the arteries or on lesions on the vessel walls. |
Atherosclerosis is a pathological process characterised by cholesterol rich lipid deposits on the internal walls (intima) of large and medium arteries (abdominal aorta, coronary arteries, arteries of the brain and legs). These deposits result in atheroma patches which provoke a thickening of the walls, the obstruction of the vessels and may be at the origin of cardiovascular attacks. (e.g. heart attacks). | |
Best-in-class | New compound in an existing drug class but which brings an additional therapeutic benefit compared to other drugs. (Increased efficiency and/or diminished side effects). |
Bioinformatics | Interdisciplinary domain, situated at the crossroads of IT, mathematics and biology, applying information technology to the biological sciences. |
Blockbusters | Medicines whose annual sales are over $ 1 billion. |
Carbohydrate | Energetic macromolecules notably containing sugars. We distinguish between simple or rapid carbohydrates and complex or slow carbohydrates, depending on the duration of digestion. |
Cardiometabolic diseases | Term to designate all cardiovascular and metabolic diseases. |
Cardiovascular diseases | The totality of illnesses affecting the heart and blood vessels characterised by several risk factors including diabetes, hypertension, obesity and dyslipidemia. The main symptoms of cardiovascular diseases are atherosclerosis, myocardial infarction, cardiac failure and stroke. |
Cell | The smallest unit which demonstrates the properties of a living being, i.e. capable of being born, developing and reproducing. |
Cholesterol | A soft, waxy substance found among the fats in the bloodstream and in all the body's cells. Cholesterol can undergo various pathways that result in the synthesis of various steroids. It is also an important determinant of membrane fluidity, and an improper amount in the body can lead to membrane instability, which leads to cell death. |
Clinical Development | Studies carried out in humans aiming to evaluate the efficiency and security of a drug candidate, under the control of the health authorities, the aim of which is to obtain an authorisation to market (see AMM). These studies normally take place in three phases. (See clinical trial) |
Diabetes | Metabolic illness characterised by abnormally high (hyperglycaemia) levels of sugar (glucose) in the blood, either at fasting or after a meal. We traditionally distinguish two main types of diabetes; type 1 diabetes, historically called insulin dependant and type 2 diabetes, historically called non-insulin dependant diabetes. |
DNA | Genetic material constituting of chromosomes and hereditary information. DNA is a macromolecule made up of two chains of nucleotides wound round each other and forming a double DNA helix. Genes are DNA segments. |
Drug candidate | Molecule in the course of study and having already successfully passed a number of pharmacological and preclinical tests and likely to obtain an authorisation to market (see AMM) after clinical trials. |
Dyslipidemia | Quantitative or qualitative anomaly of blood lipids (hypercholesterolemia, hypertriglyceridemia) constituting a major risk factor for cardiovascular illnesses. |
EMEA “European agency for the Evaluation of Medicinal Products” | European regulatory agency in charge of evaluating applications for releasing medicines on the market in the framework of a centralised procedure. The EMEA functions in a co-ordinated way with national agencies, by applying the principle of subsidiarity |
Fatty acids | The constituents of triglycerides. Fatty acids represent an important source of energy for the organism. Moreover, they have a structural role in the cell membrane and equally serve as important cellular mediators. |
FDA (Food & Drug Administration) |
Food and Drug Administration. Federal agency in the USA established to monitor clinical trials and to regulate the release of new foods and health-related products. |
Fibrates | Drug class, PPARa receptor agonists, having hypertriglyceridemia as a first indication. |
First-in-class | The initial compound in a new class of medicines. |
Functional genomics | The study of gene function, their modes of regulation, expression and their interactions. |
Gene | DNA sequence, having a precise position on a specific chromosome and which constitutes genetic information whose transmission is hereditary. Genes allow for the production of proteins by the successive phenomena of transcription and translation. |
Gene expression | Biological phenomenon corresponding to the manufacture of a RNA messenger from a gene, an intermediary element which will allow protein synthesis to happen. Synonym for transcription. |
Gene promoter | Regulating DNA region situated before a gene and containing the regulating sequences which allow the control of gene expression and amongst others, transcription factors. |
Genome | A full set of chromosomes; all the inheritable traits of an individual. |
Genomics | Scientific discipline which aims to take an inventory of all genes in a living organism and to study their functions. |
Genotype | All of the genetic material carried by an individual and constituting their genetic inheritance |
GLP | Good Laboratory Practices. International standards framing preclinical studies carried out in the laboratory during the process of developing a drug candidate and guaranteeing the quality of the conditions in which these studies are planned, carried out, managed, reported, archived and distributed. We also make reference to the recommendations of the International Conference on Harmonisation (ICH) common in the USA, Europe and Japan. |
Glycemia | Level of glucose in the blood. We speak of hypoglycaemia or hyperglycaemia when the level of glucose is abnormally low or high. |
HDL Cholesterol | Cholesterol contained in the high density lipoproteins (HDL).HDLs collect excess cholesterol in the tissues and vessel walls and bring it to the liver where it is eliminated. This is why HDL cholesterol is called “Good Cholesterol”. |
High Throughput Screening | Screening is a technique allowing the research, identification and the selection of molecules. High Throughput Screening is an automated test which consists of identifying interesting molecules out of several thousand molecules. More specifically, in the process of drug discovery, High Throughout Screening is a biological test which allows for one or more “hits” to be identified which will interact with the therapeutic target of interest. |
Hit | Chemical molecule acting on a therapeutic target, identified from screening or coming from chemical synthesis, and which constitutes the first model from which will be obtained the lead and then the future drug candidate, by the optimisation of physio-chemical and pharmacological characteristics. |
Homeostasis | Regulation mechanism by which the body tries to maintain stability in its various systems (temperature, fluid volume, mineral concentration). |
Identification of a therapeutic target | The step of finding a pertinent protein whose activity modulation will allow for a therapeutic activity in a given pathology to be obtained |
Insulin | Hormone produced by the beta cells in the pancreas (contained in the Langerhan blocks) and whose major role is to maintain a normal level of glucose in the blood. Insulin exercises hypoglycemiant effects on several metabolic tissues: the liver, skeletal muscle and fat tissue. |
Insulin-resistance | Or resistance to insulin. Incapacity of insulin "target" tissues (liver, skeletal muscle and fat tissue) to respond to the action of insulin. The step before type 2 diabetes. Not all insulin-resistant patients become diabetics. |
Insulin-secretors | Compounds or medicines which favour the secretion of insulin by the pancreas. |
Insulin sensitivity | Capacity of certain tissues (liver, skeletal muscle and fat tissue) to respond to the action of insulin. |
Insulin-sensitizers | Compounds or medicines which raise the response to insulin in the organism in the aim of lowering insulin resistance |
In vitro | Said of an experiment or a reaction which takes place in the artificial environment of a laboratory. More generally, said of experiments carried out on cell cultures. |
In vivo | Said of an experiment or an examination which is observed or carried out in a living organism (animal). |
LDL Cholesterol | Cholesterol transported by low density lipoproteins (LDL). LDL’s transport cholesterol from the liver to the organs and are at the origin of atheroma patches. This is why LDL cholesterol is called “Bad Cholesterol” |
Lead | Chemical molecule, resulting from the hit optimisation process, which responds to the precise specifications in terms of pharmacological efficacy and which will proceed to preclinical development in order to become a future drug candidate. |
Ligand | Small molecule presenting a high affinity for a given receptor and which could be at the origin of the development of a medicine. Ligands may either be agonists or antagonists. |
Lipids | A group of macromolecules made up of triglycerides and cholesterol. A qualitative or quantitative lipid anomaly or dyslipidemia constitutes a risk factor for cardiovascular diseases. |
Lipoproteins | Association formed by lipids and proteins. Lipoproteins allow lipids, which are not water soluble, to circulate in the blood (they notably ensure the transport of triglycerides and cholesterol). We distinguish between high density lipoproteins, low density lipoproteins, very low density lipoproteins and chylomicrons. |
Metabolic diseases | Very general term for all diseases which perturb the metabolism and more specifically in this document, the lipid and carbohydrate metabolism: diabetes, dyslipidemia, obesity…They may be innate (genetic) or acquired and may be due to the interruption of the synthesis chain by the absence of an enzyme, an endocrinal anomaly or nutritional imbalance. |
Metabolic pathway | Biochemical reactions linked to a product or a substrate. It includes a basic substrate and leads to the final product, with one or more intermediary modification steps between the two molecules. |
Metabolic syndrome or Syndrome X | The association of several risk factors liable to bring abour cardiovascular diseases. The definition of metabolic syndrome from the NCEP (National Cholesterol Education Program) corresponds to the existence of at least three of the following criteria:
The definition of metabolic syndrome from the WHO is slightly modified concerning glycemia after fasting equal or above 6.1 mmol/l or insulinemia after fasting in the upper quartile associated to at least two of the following criteria:
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Molecule library | Group of molecules (such as chemical compounds, peptides…) used for screening tests to “fish” for interesting molecules. |
NDA (New Drug Application) | Administrative authorisation to commercialise a drug under specific conditions. See AMM. |
Nuclear receptor | Transcription factors which also have a bond with ligands and whose activity is adjustable by small molecules. They control the expression of numerous genes implicated in diverse biological processes: metabolism, inflammation, proliferation and constitute in this sense therapeutic targets of interest. |
Obesity | Excess of fat tissue which translates as BMI (Body Mass Index) equal or superior to 30kg/m2 and which constitutes a risk factor for cardiovascular disease. The waist-hip ratio (in centimetres) is also used as a parameter of obesity. |
Peptide | Molecule formed by the joining together of amino acids (the number of amino acids is inferior to 100). The term protein is reserved for polypeptidic chains of more than 100 amino acids ; a protein being capable of being constituted of tertiary, secondary or quaternary structures. |
Pharmacogenomics | Definition 1. Discipline dedicated to the study of genetic factors which affect the action of drugs in the organism and which influence the response of the organism to them. Also known as pharmacogenetics. Definition 2. Study of the effect of a compound or a drug on gene expression. |
Pharmacokinetics | Study of the molecule in the organism. The principle steps studied are its absorption, distribution, metabolisation and elimination (ADME). Pharmacokinetic studies in animals and then in the patient allow for the construction of a quantitative model which describes these different steps according to the time elapsed and physiological parameters. This allows for the administration method and the dosage used in the clinic to be defined in order to obtain the expected therapeutic effect for the drug candidate. |
Pharmacovigilance | Discipline aiming to collect information once a drug is on the market and notably to monitor the risk of undesirable side effects resulting from their usage. |
Phase I Clinical Trial | Clinical study during which the product is administered to healthy volunteers in order to evaluate the tolerance and to measure certain pharmacokinetic parameters. |
Phase II Clinical Trial | Clinical study during which the product is administered to small groups of patients with the particular pathologies in order to determine the effective dose and to show a biological effect |
Phase III Clinical Trial | Clinical study during which the therapeutic efficacy is determined on large groups of patients, eventually comparing the drug candidate to a reference treatment. |
Phase IV Clinical Trial | Clinical study which takes place several years after a drug has been on the market and aiming to obtain additional data on the efficacy and security of the medicine. |
Phenotype | The totality of observable characters of a living being, which correspond both to the expressed part of the genotype and to the phenomena determined by the exterior environment. |
PPAR (Peroxisome Proliferator-Activated Receptor) | Sub-family of nuclear receptors notably implicated in the regulation of the lipid and carbohydrate metabolisms. We distinguish PPARa, PPARg and PPARd. |
Preclinical development | Obligatory studies carried out on leads before clinical studies and aiming to evaluate the efficacy and toxicity of these future drug candidates in different animal and cell models. |
Proteins | Macromolecules made up of polypeptide chains of at least 100 amino acids and characterised by three-dimensional secondary, tertiary and sometimes quaternary structures. One of the most important classes of molecules present in living organisms, ensuring the functioning of the cell or tissue. They are found in different forms: enzymes, hormones, receptors, transmitters… |
Proteome | The complete set of proteins from the information encoded on a genome that can be expressed and modified by a cell, tissue, or organism. |
Proteomics | A discipline for analyzing the structure, function, and interactions of the proteins produced by the genes of a particular cell, tissue, or organism, with organizing the information in databases, and with applications of the data (as in medicine or biology). |
Receptor | Protein expressed on the surface of a cell (membranous receptor) or in a cell which allows it to communicate with its environment. Every receptor is capable of establishing a specific contact with another membranous or soluble (ligand) molecule, then to send a signal to the cell’s interior, which will be followed by biological effects. |
RNA | Macromolecule formed by the association of nucleotides (ribonucleotides). RNA messengers (RNAm), which are copies of genes, serve as intermediaries in protein synthesis. |
Small Chemical Molecules | Compared to larger molecules, such as proteins or peptides, small molecules penetrate the cell membrane more easily. They may be administered orally. |
SNuRMs (Selective Nuclear Receptor Modulator) | Selective Nuclear Receptor Modulators, which allow the monitoring of their biological activity, and notably for certain nuclear receptors, the separation of beneficial effects from undesirable effects linked to their activation. |
SPPARM | Selective PPAR Modulator. |
Statin | Drug class inhibiting the synthesis of cholesterol by the inhibition of HMG-CoA reductase, an enzyme limiting the synthesis of cholesterol and leading to a lowering of plasma cholesterol. |
Stroke | Sudden loss of neurological functions caused by a cerebral attack of a ischemic or hemorrhagic nature (occlusion of a vessel by thrombosis or embolism, rupture, reduction in circulation following a drop in blood pressure, modification of the vessel…). |
Therapeutic target | Protein whose activity may be modulated by a small molecule in order to provoke a therapeutic activity targeting a given pathology ( nuclear receptors, membrane receptors, enzymes, ionic canals.) |
Transcription | Passage of genetic information from the DNA to the RNA, under the form of complimentary ribonucleotides, arising during the synthesis of single strand RNA from a DNA matrix by the action of a RNA polymerase. |
Transcription Factor | Protein which lies in a specific DNA region (more particularly on the gene promoter) in order to monitor gene expression. Transcription factors may act independently from a ligand or be controlled by a ligand (in the case of nuclear receptors). |
Transgenic | Said of an animal or vegetal organism in the cells of which foreign DNA has been introduced. |
Translation | Biological phenomenon which allows for RNAs to be transformed into proteins: the RNA messenger is used as a matrix which serves to join amino acids together to obtain a protein. |
Triglycerides | One of the two principle forms of lipids present in the organism, the other being cholesterol. Triglycerides are a type of storage of fatty acids in the organism. An abnormal rise in triglycerides, or hypertriglyceridemia, is a risk factor for cardiovascular disease. |
Type I diabetes | The more serious type of diabetes resulting from the destruction of beta cells in the pancreas (cells producing insulin) and which may appear from a very young age. An auto-immune pathology triggered in genetically predisposed people by environmental factors. This type represents 10-15% of all diabetes. |
Type 2 diabetes | The most common type of diabetes coming normally in mature adults is linked to a poor lifestyle (sedentary lifestyle, overeating…). It is a heterogeneous, non auto-immune disease which evolves. Insulin resistance precedes the diabetic state: during this phase, the pancreas compensates for this resistance by increasing its capacity to produce insulin in order to maintain normal glycemia. The diabetic state happens when the pancreas is no longer able to compensate. The pancreatic mass is diminished, a drop in insulin production and the appearance of hyperglycaemia. This represents 85-90% of all diabetes. |
Up-front payments | Payments due upon the signature of a partnership |
Validation of a therapeutic target | Experiments aiming to prove the pertinence of the specific modulation of a therapeutic target for the treatment of a disease. Traditionally, the validation of a target includes in vitro and in vivo experiments in animals. |
