In medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered and/or designed. Medicine is the art and science of healing It encompasses a range of Health care practices evolved to maintain and restore Human Health by the Biotechnology is Technology based on Biology, especially when used in Agriculture, Food science, and Medicine. Pharmacology (from Greek grc φάρμακον pharmakon, "drug" and grc -λογία -logia) is the study of how Drugs Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease
In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery. Serendipity is the effect by which one accidentally discovers something fortunate especially while looking for something else entirely A new approach has been to understand how disease and infection are controlled at the molecular and physiological level and to target specific entities based on this knowledge. A disease is an abnormal condition of an organism that impairs bodily functions and can be deadly An infection is the detrimental Colonization of a host Organism by a foreign Species. Molecular biology is the study of Biology at a molecular level Physiology (from Greek grc φύσις physis, "nature origin" and grc -λογία -logia) is the study of the mechanical physical
The process of drug discovery involves the identification of candidates, synthesis, characterization, screening, and assays for therapeutic efficacy. Once a compound has shown its value in these tests, it will begin the process of drug development prior to clinical trials. Drug development or preclinical development is defined in many pharmaceutical companies as the process of taking a new chemical lead through the stages necessary to allow it In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices
Despite advances in technology and understanding of biological systems, drug discovery is still a long process with low rate of new therapeutic discovery. Information on the human genome, its sequence and what it encodes has been hailed as a potential windfall for drug discovery, promising to virtually eliminate the bottleneck in therapeutic targets that has been one limiting factor on the rate of therapeutic discovery. The human genome is the Genome of Homo sapiens, which is stored on 23 chromosome pairs  However, data indicates that "new targets" as opposed to "established targets" are more prone to drug discovery project failure in general.  This data corroborates some thinking underlying a pharmaceutical industry trend beginning at the turn of the twenty-first century and continuing today which finds more risk aversion in target selection among multi-national pharmaceutical companies.
The definition of "target" itself is something debated within the pharmaceutical industry. However, the distinction between a "new" and "established" target can be made without a full understanding of just what a "target" is. This distinction is typically made by pharmaceutical companies engaged in discovery and development of small molecule therapeutics.
"Established targets" are those for which there is a good scientific understanding, supported by a lengthy publication history, of both how the target functions in normal physiology and how it is involved in human pathology. This does not imply that the mechanism of action of drugs that are thought to act through a particular established targets is fully understood. In Pharmacology, the term mechanism of action (MOA refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect Rather, "established" relates directly to the amount of background information available on a target, in particular functional information. The more such information is available, the less investment is (generally) required to develop a therapeutic directed against the target. The process of gathering such functional information is called "target validation" in pharmaceutical industry parlance. Established targets also include those that the pharmaceutical industry has had experience mounting drug discovery campaigns against in the past; such a history provides information on the chemical feasibility of developing a small molecular therapeutic against the target and can provide licensing opportunities and freedom-to-operate indicators with respect to small molecule therapeutic candidates.
In general, "new targets" are all those targets that are not "established targets" but which have been or are the subject of drug discovery campaigns. These typically include newly discovered proteins, or proteins whose function has now become clear as a result of basic scientific research. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl
The majority of targets currently selected for drug discovery efforts are proteins. Two classes predominate: G-protein-coupled receptors (or GPCRs) and protein kinases. G protein-coupled receptors ( GPCRs) also known as seven transmembrane domain receptors, 7TM receptors, heptahelical receptors, and A protein kinase is a Kinase Enzyme that modifies other Proteins by chemically adding Phosphate groups to them ( Phosphorylation)
The process of finding a new drug against a chosen target for a particular disease usually involves high-throughput screening (HTS), wherein large libraries of chemicals are tested for their ability to modify the target. High-throughput screening (HTS is a method for scientific Experimentation especially used in Drug discovery and relevant to the fields of Biology and For example, if the target is a novel GPCR, compounds will be screened for their ability to inhibit or stimulate that receptor (see antagonist and agonist): if the target is a protein kinase, the chemicals will be tested for their ability to inhibit that kinase. G protein-coupled receptors ( GPCRs) also known as seven transmembrane domain receptors, 7TM receptors, heptahelical receptors, and A receptor antagonist is a type of receptor ligand or Drug that does not provoke a biological response itself upon binding to a receptor, but blocks An agonist is a term used to describe a type of ligand or drug that binds and alters the activity of a receptor. A protein kinase is a Kinase Enzyme that modifies other Proteins by chemically adding Phosphate groups to them ( Phosphorylation) Enzyme inhibitors are Molecules that bind to Enzymes and decrease their activity.
Another important function of HTS is to show how selective the compounds are for the chosen target. The ideal is to find a molecule which will interfere with only the chosen target, but not other, related targets. To this end, other screening runs will be made to see whether the "hits" against the chosen target will interfere with other related targets - this is the process of cross-screening. Cross-screening is important, because the more unrelated targets a compound hits, the more likely that off-target toxicity will occur with that compound once it reaches the clinic. Toxicity is the degree to which a substance is able to damage an exposed organism
It is very unlikely that a perfect drug candidate will emerge from these early screening runs. It is more often observed that several compounds are found to have some degree of activity, and if these compounds share common chemical features, one or more pharmacophores can then be developed. Pharmacological or biological activity is an expression describing the beneficial or adverse effects of a Drug on living matter. A pharmacophore was first defined by Paul Ehrlich in 1909 as "a molecular framework that carries ( phoros) the essential features responsible for a At this point, medicinal chemists will attempt to use structure-activity relationships (SAR) to improve certain features of the lead compound:
This process will require several iterative screening runs, during which, it is hoped, the properties of the new molecular entities will improve, and allow the favoured compounds to go forward to in vitro and in vivo testing for activity in the disease model of choice. In vitro ( Latin: within the glass refers to the technique of performing a given experiment in a controlled environment outside of a living Organism In vivo ( Latin: within the living means that which takes place inside an organism.
While HTS is a commonly used method for novel drug discovery, it is not the only method. It is often possible to start from a molecule which already has some of the desired properties. Such a molecule might be extracted from a natural product or even be a drug on the market which could be improved upon (so-called "me too" drugs). A natural product is a Chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical Other methods, such as virtual high throughput screening, where screening is done using computer-generated models and attempting to "dock" virtual libraries to a target, are also often used. Virtual high throughput screening or virtual screening is a computational technique used in Drug discovery research
Another important method for drug discovery is drug design, whereby the biological and physical properties of the target are studied, and a prediction is made of the sorts of chemicals that might (eg. Drug design is the approach of finding drugs by design based on their Biological targets Typically a drug target is a key Molecule involved in a particular ) fit into an active site. The active site of an Enzyme contains the catalytic and Binding sites. Novel pharmacophores can emerge very rapidly from these exercises.
Once a lead compound series has been established with sufficient target potency and selectivity and favourable drug-like properties, one or two compounds will then be proposed for drug development. Drug development or preclinical development is defined in many pharmaceutical companies as the process of taking a new chemical lead through the stages necessary to allow it The best of these is generally called the lead compound, while the other will be designated as the "backup". A lead compound (ie the "leading" compound not Lead metal in Drug discovery is a Chemical compound that has pharmacological or
1. Early Drug discovery involves several phases from target identification to preclinical development Drug development or preclinical development is defined in many pharmaceutical companies as the process of taking a new chemical lead through the stages necessary to allow it Pre-clinical development is a stage of research that begins before Clinical trials (testing in humans can begin and during which important feasibility iterative testing and Protein structure prediction is one of the most important goals pursued by Bioinformatics and Theoretical chemistry. Drug design is the approach of finding drugs by design based on their Biological targets Typically a drug target is a key Molecule involved in a particular Drug design is the approach of finding drugs by design based on their Biological targets Typically a drug target is a key Molecule involved in a particular Maria rulesDrug discovery depends on methods by which many different chemicals are assayed for their activity Bioinformatics is the application of information technology to the field of molecular biology Cheminformatics (also known as chemoinformatics and chemical informatics) is the use of computer and informational techniques applied to a range of problems Biomedical informatics is the broad discipline concerned with the study and application of Computer science, Information science, Informatics, Cognitive In the US, an orphan drug is any drug developed under the Orphan Drug Act of January 1983 ("ODA" a Federal law concerning Rare diseases Physiologically-based pharmacokinetic modeling ( PBPK) is a Mathematical modeling technique for prediction of the absorption distribution metabolization and excretion The Simcyp population-based ADME simulator is a modelling and simulation platform used by the pharmaceutical industry in drug discovery and development The terms Pharmacogenomics and pharmacogenetics tend to be used interchangeably and a precise consensus definition of either remains elusive Molecular modelling is a collective term that refers to theoretical methods and computational techniques to model or mimic the behaviour of Molecules The techniques Shayne Cox Gad (2005), Drug Discovery Handbook, Wiley-Interscience, ISBN 0-471-21384-5
2. Madsen U. (2002), Textbook of Drug Design and Discovery, CRC, ISBN 0-415-28288-8