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Drug discovery

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Digoxin (better known as Digitalis ), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions . Most frequently it is used for atrial fibrillation , atrial flutter , and heart failure . Digoxin is one of the oldest medications used in the field of cardiology . It works by increasing myocardial contractility , increasing stroke volume and blood pressure , reducing heart rate , and somewhat extending the time frame of the contraction . Digoxin is taken by mouth or by injection into a vein . Digoxin has a half life of approximately 36 hours given at average doses in patients with normal renal function. It is excreted mostly unchanged in the urine.

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140-487: In the fields of medicine, biotechnology , and pharmacology , drug discovery is the process by which new candidate medications are discovered. Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by serendipitous discovery, as with penicillin . More recently, chemical libraries of synthetic small molecules , natural products , or extracts were screened in intact cells or whole organisms to identify substances that had

280-491: A herbicide ), reduction of spoilage, or improving the nutrient profile of the crop. Examples in non-food crops include production of pharmaceutical agents , biofuels , and other industrially useful goods, as well as for bioremediation . Farmers have widely adopted GM technology. Between 1996 and 2011, the total surface area of land cultivated with GM crops had increased by a factor of 94, from 17,000 to 1,600,000 square kilometers (4,200,000 to 395,400,000 acres). 10% of

420-474: A plasmid vector inserted into the bacterium Escherichia coli . Insulin, widely used for the treatment of diabetes, was previously extracted from the pancreas of abattoir animals (cattle or pigs). The genetically engineered bacteria are able to produce large quantities of synthetic human insulin at relatively low cost. Biotechnology has also enabled emerging therapeutics like gene therapy . The application of biotechnology to basic science (for example through

560-668: A Unified Database System) database is intended to help companies, interested private users and competent authorities to find precise information on the presence, detection and identification of GMOs used in the European Union . The information is provided in English. In 1988, after prompting from the United States Congress , the National Institute of General Medical Sciences ( National Institutes of Health ) (NIGMS) instituted

700-455: A bacterium (of the genus Pseudomonas ) capable of breaking down crude oil, which he proposed to use in treating oil spills. (Chakrabarty's work did not involve gene manipulation but rather the transfer of entire organelles between strains of the Pseudomonas bacterium). The MOSFET invented at Bell Labs between 1955 and 1960, Two years later, Leland C. Clark and Champ Lyons invented

840-438: A child's parentage (genetic mother and father) or in general a person's ancestry . In addition to studying chromosomes to the level of individual genes, genetic testing in a broader sense includes biochemical tests for the possible presence of genetic diseases, or mutant forms of genes associated with increased risk of developing genetic disorders. Genetic testing identifies changes in chromosomes , genes, or proteins. Most of

980-503: A compound hits, the more likely that off-target toxicity will occur with that compound once it reaches the clinic. It is unlikely that a perfect drug candidate will emerge from these early screening runs. One of the first steps is to screen for compounds that are unlikely to be developed into drugs; for example compounds that are hits in almost every assay, classified by medicinal chemists as " pan-assay interference compounds ", are removed at this stage, if they were not already removed from

1120-413: A consortium could be used as industrial microbes to produce precursors of the chemotherapeutic agent paclitaxel by applying the metabolic engineering in a co-culture approach to exploit the benefits from the two microbes. Another example of synthetic biology applications in industrial biotechnology is the re-engineering of the metabolic pathways of E. coli by CRISPR and CRISPRi systems toward

1260-540: A desirable therapeutic effect in a process known as classical pharmacology . After sequencing of the human genome allowed rapid cloning and synthesis of large quantities of purified proteins, it has become common practice to use high throughput screening of large compounds libraries against isolated biological targets which are hypothesized to be disease-modifying in a process known as reverse pharmacology . Hits from these screens are then tested in cells and then in animals for efficacy . Modern drug discovery involves

1400-579: A drug is developed with evidence throughout its history of research to show it is safe and effective for the intended use in the United States, the company can file an application – the New Drug Application (NDA) – to have the drug commercialized and available for clinical application. NDA status enables the FDA to examine all submitted data on the drug to reach a decision on whether to approve or not approve

1540-422: A drug's efficacy or toxicity . The purpose of pharmacogenomics is to develop rational means to optimize drug therapy, with respect to the patients' genotype , to ensure maximum efficacy with minimal adverse effects . Such approaches promise the advent of " personalized medicine "; in which drugs and drug combinations are optimized for each individual's unique genetic makeup. Biotechnology has contributed to

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1680-408: A drug, it has been suggested that natural products compare favourably to today's combinatorial chemistry libraries as potential lead molecules. Two main approaches exist for the finding of new bioactive chemical entities from natural sources. The first is sometimes referred to as random collection and screening of material, but the collection is far from random. Biological (often botanical) knowledge

1820-410: A food source into another form. Before the time of Charles Darwin 's work and life, animal and plant scientists had already used selective breeding. Darwin added to that body of work with his scientific observations about the ability of science to change species. These accounts contributed to Darwin's theory of natural selection. For thousands of years, humans have used selective breeding to improve

1960-417: A funding mechanism for biotechnology training. Universities nationwide compete for these funds to establish Biotechnology Training Programs (BTPs). Each successful application is generally funded for five years then must be competitively renewed. Graduate students in turn compete for acceptance into a BTP; if accepted, then stipend, tuition and health insurance support are provided for two or three years during

2100-475: A guide to improve the potency and properties of new drug leads. There is also a paradigm shift in the drug discovery community to shift away from HTS, which is expensive and may only cover limited chemical space , to the screening of smaller libraries (maximum a few thousand compounds). These include fragment-based lead discovery (FBDD) and protein-directed dynamic combinatorial chemistry . The ligands in these approaches are usually much smaller, and they bind to

2240-536: A harmful microbe are examples of environmental implications of biotechnology. Many cities have installed CityTrees , which use biotechnology to filter pollutants from urban atmospheres. The regulation of genetic engineering concerns approaches taken by governments to assess and manage the risks associated with the use of genetic engineering technology, and the development and release of genetically modified organisms (GMO), including genetically modified crops and genetically modified fish . There are differences in

2380-419: A known physiological/pathological pathway, avoiding the mass screening of banks of stored compounds. This led to great success, such as the work of Gertrude Elion and George H. Hitchings on purine metabolism , the work of James Black on beta blockers and cimetidine , and the discovery of statins by Akira Endo . Another champion of the approach of developing chemical analogues of known active substances

2520-489: A large chemical space when compared to HTS. Phenotypic screens have also provided new chemical starting points in drug discovery.  A variety of models have been used including yeast, zebrafish, worms, immortalized cell lines, primary cell lines, patient-derived cell lines and whole animal models. These screens are designed to find compounds which reverse a disease phenotype such as death, protein aggregation, mutant protein expression, or cell proliferation as examples in

2660-533: 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 . The best of these is generally called the lead compound , while the other will be designated as the "backup". These decisions are generally supported by computational modelling innovations. Traditionally, many drugs and other chemicals with biological activity have been discovered by studying chemicals that organisms create to affect

2800-456: A more holistic cell model or organism. Smaller screening sets are often used for these screens, especially when the models are expensive or time-consuming to run.  In many cases, the exact mechanism of action of hits from these screens is unknown and may require extensive target deconvolution experiments to ascertain. The growth of the field of chemoproteomics has provided numerous strategies to identify drug targets in these cases. Once

2940-458: A new drug approval process, called the New Drug Application in the United States. Discovering drugs that may be a commercial success, or a public health success, involves a complex interaction between investors, industry, academia, patent laws , regulatory exclusivity, marketing , and the need to balance secrecy with communication. Meanwhile, for disorders whose rarity means that no large commercial success or public health effect can be expected,

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3080-415: A notable advance in comparison with the lack of studies published in recent years in scientific journals by those companies. Krimsky, Sheldon (2015). "An Illusory Consensus behind GMO Health Assessment". Science, Technology, & Human Values . 40 (6): 883–914. doi : 10.1177/0162243915598381 . S2CID   40855100 . I began this article with the testimonials from respected scientists that there

3220-513: A number of articles some of which have strongly and negatively influenced the public opinion on GM crops and even provoked political actions, such as GMO embargo, share common flaws in the statistical evaluation of the data. Having accounted for these flaws, we conclude that the data presented in these articles does not provide any substantial evidence of GMO harm. The presented articles suggesting possible harm of GMOs received high public attention. However, despite their claims, they actually weaken

3360-434: A number of ecological benefits, if not used in excess. Insect-resistant crops have proven to lower pesticide usage, therefore reducing the environmental impact of pesticides as a whole. However, opponents have objected to GM crops per se on several grounds, including environmental concerns, whether food produced from GM crops is safe, whether GM crops are needed to address the world's food needs, and economic concerns raised by

3500-459: A particular disease usually involves high-throughput screening (HTS), wherein large libraries of chemicals are tested for their ability to modify the target. 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. Another function of HTS

3640-594: A promising method to combat malnutrition in India and other countries. Industrial biotechnology (known mainly in Europe as white biotechnology) is the application of biotechnology for industrial purposes, including industrial fermentation . It includes the practice of using cells such as microorganisms , or components of cells like enzymes , to generate industrially useful products in sectors such as chemicals, food and feed, detergents, paper and pulp, textiles and biofuels . In

3780-471: A pure microbiological culture in an industrial process, that of manufacturing corn starch using Clostridium acetobutylicum , to produce acetone , which the United Kingdom desperately needed to manufacture explosives during World War I . Biotechnology has also led to the development of antibiotics. In 1928, Alexander Fleming discovered the mold Penicillium . His work led to the purification of

3920-497: A reduced digoxin metabolite profile correlates with E. lenta abundance. Further studies have also revealed an increase in digoxin toxicity when used alongside erythromycin or tetracycline , the researches attributed this to the decrease in the E. lenta population. Derivatives of plants of the genus Digitalis have a long history of medical use. Nicholas Culpeper referred to various medical uses for Foxglove in his 1652 publication The English physician . William Withering

4060-557: A shortened QT interval. Also, the T wave may be inverted and accompanied by ST depression. It may cause AV junctional rhythm and ectopic beats (bigeminy) resulting in ventricular tachycardia and fibrillation . Digoxin is also an M2 receptor muscarinic agonist . Digoxin is usually given orally, but can also be given by IV injection in urgent situations (the IV injection should be slow, and heart rhythm should be monitored). While IV therapy may be better tolerated (less nausea), digoxin has

4200-446: A target, are also often used. Another method for drug discovery is de novo drug design , in which a prediction is made of the sorts of chemicals that might (e.g.) fit into an active site of the target enzyme. For example, virtual screening and computer-aided drug design are often used to identify new chemical moieties that may interact with a target protein. Molecular modelling and molecular dynamics simulations can be used as

4340-404: A target, in particular functional information. In general, "new targets" are all those targets that are not "established targets" but which have been or are the subject of drug discovery efforts. The majority of targets selected for drug discovery efforts are proteins, such as G-protein-coupled receptors (GPCRs) and protein kinases . The process of finding a new drug against a chosen target for

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4480-594: A very long distribution half-life into the cardiac tissue, which will delay its onset of action by a number of hours. The half-life is about 36 hours for patients with normal renal function , digoxin is given once daily, usually in 125 μg or 250 μg doses. Digoxin elimination is mainly by renal excretion and involves P-glycoprotein , which leads to significant clinical interactions with P-glycoprotein inhibitor drugs. Examples commonly used in patients with heart problems include spironolactone , verapamil and amiodarone . In patients with decreased kidney function

4620-414: A wide range of procedures for modifying living organisms for human purposes, going back to domestication of animals, cultivation of plants, and "improvements" to these through breeding programs that employ artificial selection and hybridization . Modern usage also includes genetic engineering, as well as cell and tissue culture technologies. The American Chemical Society defines biotechnology as

4760-448: Is genetic engineering , which allows scientists to modify the genetic makeup of organisms to achieve desired outcomes. This can involve inserting genes from one organism into another, and consequently, create new traits or modifying existing ones. Other important techniques used in biotechnology include tissue culture, which allows researchers to grow cells and tissues in the lab for research and medical purposes, and fermentation , which

4900-437: Is a portmanteau , derived from Digitalis lanata and toxin . In 1930, Digoxin was first isolated by Dr. Sydney Smith from the foxglove plant, Digitalis lanata . Initially, the digoxin was purified by dissolving the dried plant material in acetone and boiling the solution in chloroform. The solution was then reacted with acetic acid and small amount of ferric chloride and sulfuric acid ( Keller reaction ). Digoxin

5040-483: 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). Other methods, such as virtual high throughput screening , where screening is done using computer-generated models and attempting to "dock" virtual libraries to

5180-413: 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 target is fully understood. Rather, "established" relates directly to the amount of background information available on

5320-507: Is a rapidly evolving field with significant potential to address pressing global challenges and improve the quality of life for people around the world; however, despite its numerous benefits, it also poses ethical and societal challenges, such as questions around genetic modification and intellectual property rights . As a result, there is ongoing debate and regulation surrounding the use and application of biotechnology in various industries and fields. The concept of biotechnology encompasses

5460-431: Is also used intrafetally or amniotically during abortions in the late second trimester and third trimester of pregnancy. It typically causes fetal demise (measured by cessation of cardiac activity) within hours of administration. The occurrence of adverse drug reactions is common, owing to its narrow therapeutic index (the margin between effectiveness and toxicity ). Gynaecomastia (enlargement of breast tissue )

5600-1061: Is based on post hoc analysis of prospective trials, suggesting higher levels may be associated with increased mortality rates . For heart rate control ( atrial fibrillation ), plasma levels are less defined and are generally titrated to a goal heart rate. Typically, digoxin levels are considered therapeutic for heart rate control between 0.5 and 2.0 ng/mL (or 0.6 and 2.6 nmol/L). In suspected toxicity or ineffectiveness, digoxin levels should be monitored. Plasma potassium levels also need to be closely controlled (see side effects, below). Quinidine , verapamil , and amiodarone increase plasma levels of digoxin (by displacing tissue binding sites and depressing renal digoxin clearance), so plasma digoxin must be monitored carefully when coadministered. A study which looked to see if digoxin affected men and women differently found that digoxin did not reduce deaths overall, but did result in less hospitalization. Women who took digoxin died "more frequently" (33%) than women who took placebo (29%). Digoxin increased

5740-635: Is based on the basic biological sciences (e.g., molecular biology , biochemistry , cell biology , embryology , genetics , microbiology ) and conversely provides methods to support and perform basic research in biology. Biotechnology is the research and development in the laboratory using bioinformatics for exploration, extraction, exploitation, and production from any living organisms and any source of biomass by means of biochemical engineering where high value-added products could be planned (reproduced by biosynthesis , for example), forecasted, formulated, developed, manufactured, and marketed for

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5880-638: Is considered one of the essential cornerstones in industrial biotechnology due to its financial and sustainable contribution to the manufacturing sector. Jointly biotechnology and synthetic biology play a crucial role in generating cost-effective products with nature-friendly features by using bio-based production instead of fossil-based. Synthetic biology can be used to engineer model microorganisms , such as Escherichia coli , by genome editing tools to enhance their ability to produce bio-based products, such as bioproduction of medicines and biofuels . For instance, E. coli and Saccharomyces cerevisiae in

6020-501: Is credited with the first published description of the systematic use of Digitalis derivatives in his 1785 book An Account of the Foxglove and some of its Medical Uses With Practical Remarks on Dropsy and Other Diseases . Its use was somewhat sporadic until Sir James Mackenzie identified the phenomenon of atrial fibrillation , and the actions of digitalis on this. Its effects were first explained by Arthur Robertson Cushny . The name

6160-859: Is expected to be good news for the biotechnology sector, with the Department of Energy estimating ethanol usage could reduce U.S. petroleum-derived fuel consumption by up to 30% by 2030. The biotechnology sector has allowed the U.S. farming industry to rapidly increase its supply of corn and soybeans—the main inputs into biofuels—by developing genetically modified seeds that resist pests and drought. By increasing farm productivity, biotechnology boosts biofuel production. Biotechnology has applications in four major industrial areas, including health care (medical), crop production and agriculture, non-food (industrial) uses of crops and other products (e.g., biodegradable plastics , vegetable oil , biofuels ), and environmental uses. For example, one application of biotechnology

6300-415: 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. Amongst the physicochemical properties associated with drug absorption include ionization (pKa), and solubility; permeability can be determined by PAMPA and Caco-2 . PAMPA is attractive as an early screen due to

6440-453: Is increased, resulting in a net increase in blood pressure , leading to increased tissue perfusion . This causes the myocardium to work more efficiently, with optimized hemodynamics and an improved ventricular function curve. Other electrical effects include a brief initial increase in action potential , followed by a decrease as the K conductance increases due to increased intracellular amounts of Ca ions. The refractory period of

6580-405: Is known as reverse pharmacology and is the most frequently used approach today. In the 2020s, qubit and quantum computing started to be used to reduce the time needed to drug discovery. A "target" is produced within the pharmaceutical industry. Generally, the "target" is the naturally existing cellular or molecular structure involved in the pathology of interest where the drug-in-development

6720-565: Is literally no scientific controversy over the health effects of GMOs. My investigation into the scientific literature tells another story. And contrast: Panchin, Alexander Y.; Tuzhikov, Alexander I. (January 14, 2016). "Published GMO studies find no evidence of harm when corrected for multiple comparisons". Critical Reviews in Biotechnology . 37 (2): 213–217. doi : 10.3109/07388551.2015.1130684 . ISSN   0738-8551 . PMID   26767435 . S2CID   11786594 . Here, we show that

6860-441: Is meant to act. 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 the discovery and development of therapeutics. In an estimate from 2011, 435 human genome products were identified as therapeutic drug targets of FDA-approved drugs. "Established targets" are those for which there

7000-410: Is mentioned in many textbooks as a side effect, thought to be due to the estrogen -like steroid moiety of the digoxin molecule, but when systematically sought, the evidence for this is equivocal as of 2005 . The combination of increased ( atrial ) arrhythmogenesis and inhibited atrioventricular (AV) conduction (for example paroxysmal atrial tachycardia with AV block – so-called "PAT with block")

7140-928: Is not effective at reducing cancer risk at therapeutic concentrations of the drug, so the results need further investigation. Digoxin preparations are marketed under the brand names Cardigox; Cardiogoxin; Cardioxin; Cardoxin; Coragoxine; Digacin; Digicor; Digitek; Digomal; Digon; Digosin; Digoxine Navtivelle; Digoxina-Sandoz; Digoxin-Sandoz; Digoxin-Zori; Dilanacin; Eudigox; Fargoxin; Grexin; Lanacordin; Lanacrist; Lanicor; Lanikor; Lanorale; Lanoxicaps; Lanoxin; Lanoxin PG; Lenoxicaps; Lenoxin; Lifusin; Mapluxin; Natigoxin; Novodigal; Purgoxin; Sigmaxin; Sigmaxin-PG; Toloxin. Cardiac glycosides, particularly digoxin, have been conventionally used for treatment of common cardiac problems, mainly heart failure and cardiac arrhythmias. The interaction of digoxin and cancer has also been studied. Despite existence of numerous preclinical studies that investigated

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7280-481: Is not eligible for parole . On April 25, 2008, the U.S. Food and Drug Administration (FDA) issued a press release alerting the public to a Class I recall of Digitek, a brand of digoxin produced by Mylan . Some tablets had been released at double thickness and therefore double strength, causing some patients to experience digoxin toxicity. A class-action lawsuit against the Icelandic generic drug maker Actavis

7420-639: Is now an option for drug developers. AI algorithms are being used to perform virtual screening of chemical compounds, which involves predicting the activity of a compound against a specific target. By using machine learning algorithms to analyse large amounts of chemical data, researchers can identify potential new drug candidates that are more likely to be effective against a specific disease. Algorithms, such as Nearest-Neighbour classifiers, RF, extreme learning machines, SVMs, and deep neural networks (DNNs), are used for VS based on synthesis feasibility and can also predict in vivo activity and toxicity. The elucidation of

7560-532: Is often used to identify families that show promise. This approach is effective because only a small part of the earth's biodiversity has ever been tested for pharmaceutical activity. Also, organisms living in a species-rich environment need to evolve defensive and competitive mechanisms to survive. Those mechanisms might be exploited in the development of beneficial drugs. A collection of plant, animal and microbial samples from rich ecosystems can potentially give rise to novel biological activities worth exploiting in

7700-472: Is required in older people and those with poor kidney function . It is unclear whether use during pregnancy is safe. Digoxin is in the cardiac glycoside family of medications. It was first isolated in 1930 from the foxglove plant, Digitalis lanata . It is on the World Health Organization's List of Essential Medicines . In 2021, it was the 241st most commonly prescribed medication in

7840-428: Is said to be pathognomonic (that is, diagnostic) of digoxin toxicity. Digoxin can lead to cardiac arrhythmias when given with thiazides and loop diuretics. This is because co-administration of Digoxin with drugs such as thiazides and loop diuretics which can cause hypokalemia , low serum levels of potassium in the blood. This exacerbates the potential for cardiac arrhythmias because the low levels of potassium reduces

7980-673: Is the application of the principles of engineering and natural sciences to tissues, cells, and molecules. This can be considered as the use of knowledge from working with and manipulating biology to achieve a result that can improve functions in plants and animals. Relatedly, biomedical engineering is an overlapping field that often draws upon and applies biotechnology (by various definitions), especially in certain sub-fields of biomedical or chemical engineering such as tissue engineering , biopharmaceutical engineering , and genetic engineering . Although not normally what first comes to mind, many forms of human-derived agriculture clearly fit

8120-708: Is the directed use of microorganisms for the manufacture of organic products (examples include beer and milk products). Another example is using naturally present bacteria by the mining industry in bioleaching . Biotechnology is also used to recycle, treat waste, clean up sites contaminated by industrial activities ( bioremediation ), and also to produce biological weapons . A series of derived terms have been coined to identify several branches of biotechnology, for example: In medicine, modern biotechnology has many applications in areas such as pharmaceutical drug discoveries and production, pharmacogenomics , and genetic testing (or genetic screening ). In 2021, nearly 40% of

8260-403: Is thus usually a capital-intensive process that involves large investments by pharmaceutical industry corporations as well as national governments (who provide grants and loan guarantees ). Despite advances in technology and understanding of biological systems, drug discovery is still a lengthy, "expensive, difficult, and inefficient process" with low rate of new therapeutic discovery. In 2010,

8400-423: Is to show how selective the compounds are for the chosen target, as one wants 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 useful because the more unrelated targets

8540-442: Is used to produce a wide range of products such as beer, wine, and cheese. The applications of biotechnology are diverse and have led to the development of essential products like life-saving drugs, biofuels , genetically modified crops, and innovative materials. It has also been used to address environmental challenges, such as developing biodegradable plastics and using microorganisms to clean up contaminated sites. Biotechnology

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8680-488: Is widely used in biomedical applications, such as the detection of DNA hybridization , biomarker detection from blood , antibody detection, glucose measurement, pH sensing, and genetic technology . By the mid-1980s, other BioFETs had been developed, including the gas sensor FET (GASFET), pressure sensor FET (PRESSFET), chemical field-effect transistor (ChemFET), reference ISFET (REFET), enzyme-modified FET (ENFET) and immunologically modified FET (IMFET). By

8820-631: The DNA of which has been modified with genetic engineering techniques. In most cases, the main aim is to introduce a new trait that does not occur naturally in the species. Biotechnology firms can contribute to future food security by improving the nutrition and viability of urban agriculture. Furthermore, the protection of intellectual property rights encourages private sector investment in agrobiotechnology. Examples in food crops include resistance to certain pests, diseases, stressful environmental conditions, resistance to chemical treatments (e.g. resistance to

8960-461: The Human Genome Project ) has also dramatically improved our understanding of biology and as our scientific knowledge of normal and disease biology has increased, our ability to develop new medicines to treat previously untreatable diseases has increased as well. Genetic testing allows the genetic diagnosis of vulnerabilities to inherited diseases , and can also be used to determine

9100-510: The anticoagulant drugs, hirudin and its synthetic congener , bivalirudin , are based on saliva chemistry of the leech , Hirudo medicinalis . Used to treat type 2 diabetes , exenatide was developed from saliva compounds of the Gila monster , a venomous lizard . Microbes compete for living space and nutrients. To survive in these conditions, many microbes have developed abilities to prevent competing species from proliferating. Microbes are

9240-578: The atria and ventricles is decreased, while it increases in the sinoatrial and AV nodes. A less negative resting membrane potential is made, leading to increased irritability. The conduction velocity increases in the atria, but decreases in the AV node. The effect upon Purkinje fibers and ventricles is negligible. Automaticity is also increased in the atria , AV node, Purkinje fibers , and ventricles. ECG changes seen in people taking digoxin include increased PR interval (due to decreased AV conduction) and

9380-407: The cardiac action potential , which leads to a decrease in heart rate. Increased amounts of Ca also leads to increased storage of calcium in the sarcoplasmic reticulum , causing a corresponding increase in the release of calcium during each action potential. This leads to increased contractility (the force of contraction) of the heart without increasing heart energy expenditure. The inhibition of

9520-414: The chemical space based on their physicochemical characteristics, is often used to describe the difference between the combinatorial chemistry libraries and natural products. The synthetic, combinatorial library compounds seem to cover only a limited and quite uniform chemical space, whereas existing drugs and particularly natural products, exhibit much greater chemical diversity, distributing more evenly to

9660-405: The orphan drug funding process ensures that people who experience those disorders can have some hope of pharmacotherapeutic advances. The idea that the effect of a drug in the human body is mediated by specific interactions of the drug molecule with biological macromolecules, ( proteins or nucleic acids in most cases) led scientists to the conclusion that individual chemicals are required for

9800-430: The research and development cost of each new molecular entity was about US$ 1.8 billion. In the 21st century, basic discovery research is funded primarily by governments and by philanthropic organizations, while late-stage development is funded primarily by pharmaceutical companies or venture capitalists. To be allowed to come to market, drugs must undergo several successful phases of clinical trials, and pass through

9940-540: The sodium pump may also improve baroreceptor sensitivity in heart failure and may explain some of the neurohormonal effects of digoxin. Digoxin also has important parasympathetic effects, particularly on the atrioventricular node . While it does increase the magnitude of myocardial contractility, the duration of the contraction is only slightly increased. Its use as an antiarrhythmic drug , then, comes from its direct and indirect parasympathetic stimulating properties. Vagus nerve stimulation slows down conduction at

10080-422: The AV node by increasing the refractory period of cardiac myocytes. The slowed AV node gives the ventricles more time to fill before contracting. This negative chronotropic effect is synergistic with the direct effect on cardiac pacemaker cells. The arrhythmia itself is not affected, but the pumping function of the heart improves, owing to improved filling. Overall, the heart rate is decreased while stroke volume

10220-665: The ECM. The discovery of JADs on skin repair has introduced newfound interest in the effects of these plant hormones in therapeutic medicinal application. Salicylic acid (SA), a phytohormone , was initially derived from willow bark and has since been identified in many species. It is an important player in plant immunity , although its role is still not fully understood by scientists. They are involved in disease and immunity responses in plant and animal tissues. They have salicylic acid binding proteins (SABPs) that have shown to affect multiple animal tissues. The first discovered medicinal properties of

10360-455: The EU and approval for import and processing. While only a few GMOs have been approved for cultivation in the EU a number of GMOs have been approved for import and processing. The cultivation of GMOs has triggered a debate about the coexistence of GM and non-GM crops. Depending on the coexistence regulations, incentives for the cultivation of GM crops differ. The EUginius (European GMO Initiative for

10500-835: The United States, with more than 1   million prescriptions. The most common indications for digoxin are atrial fibrillation and atrial flutter with rapid ventricular response, especially in older or less active patients, though beta blockers and/or calcium channel blockers may be preferred in some patients, such as younger more active ones, or those without heart failure or hemodynamic instability. Early observational studies showed an increased risk of death in patients taking digoxin, despite an attempt to allow for other risk factors for death (so-called propensity score matching ). However, systematic reviews focusing on randomised controlled trials of digoxin (which ensured similarity between patients on digoxin, and those not on it) showed no difference in mortality. Evidence suggested

10640-505: The ability to directly act on mitochondrial membranes by inducing membrane depolarization via release of metabolites . Jasmonate derivatives (JAD) are also important in wound response and tissue regeneration in plant cells. They have also been identified to have anti-aging effects on human epidermal layer. It is suspected that they interact with proteoglycans (PG) and glycosaminoglycan (GAG) polysaccharides , which are essential extracellular matrix (ECM) components to help remodel

10780-517: The activity of other organisms for survival. Despite the rise of combinatorial chemistry as an integral part of lead discovery process, natural products still play a major role as starting material for drug discovery. A 2007 report found that of the 974 small molecule new chemical entities developed between 1981 and 2006, 63% were natural derived or semisynthetic derivatives of natural products . For certain therapy areas, such as antimicrobials, antineoplastics, antihypertensive and anti-inflammatory drugs,

10920-550: The amount of K+ at the ATPase pump and increase calcium levels too much which leads to these arrhythmias. It can also cause visual disturbances as well as dizziness or fainting. Several other drugs associated with ADRs in concomitant use include verapamil, amiodarone, quinidine, tetracycline, and erythromycin. In overdose, the usual supportive measures are needed. If arrhythmias prove troublesome, or malignant hyperkalemia occurs (inexorably rising potassium level due to paralysis of

11060-435: The amount of digoxin in the body decreases quickly as it gets excreted rapidly. Digoxin's primary mechanism of action involves inhibition of the sodium potassium adenosine triphosphatase ( Na+/K+ ATPase ), mainly in the myocardium . This inhibition causes an increase in intracellular sodium levels, resulting in decreased activity of the sodium-calcium exchanger , which normally imports three extracellular sodium ions into

11200-518: The antibiotic compound formed by the mold by Howard Florey , Ernst Boris Chain and Norman Heatley – to form what we today know as penicillin . In 1940, penicillin became available for medicinal use to treat bacterial infections in humans. The field of modern biotechnology is generally thought of as having been born in 1971 when Paul Berg's (Stanford) experiments in gene splicing had early success. Herbert W. Boyer (Univ. Calif. at San Francisco) and Stanley N. Cohen (Stanford) significantly advanced

11340-478: The anticancer effects of digoxin, there are no solid and conclusive results so far. Several studies have suggested that digoxin may have anticancer properties, others not. Digoxin, as a cardiac glycoside, has a chemical structure basically similar to that of estradiol . Digoxin has the ability to bind oestrogen receptors, and therefore it has been proposed that it might increase the risk of oestrogen-sensitive breast and uterine cancers. A large Danish study found

11480-502: The application of biological organisms, systems, or processes by various industries to learning about the science of life and the improvement of the value of materials and organisms, such as pharmaceuticals, crops, and livestock . As per the European Federation of Biotechnology , biotechnology is the integration of natural science and organisms, cells, parts thereof, and molecular analogues for products and services. Biotechnology

11620-401: The biological activity of the drug. This made for the beginning of the modern era in pharmacology , as pure chemicals, instead of crude extracts of medicinal plants , became the standard drugs. Examples of drug compounds isolated from crude preparations are morphine , the active agent in opium, and digoxin , a heart stimulant originating from Digitalis lanata . Organic chemistry also led to

11760-462: The broad definition of "utilizing a biotechnological system to make products". Indeed, the cultivation of plants may be viewed as the earliest biotechnological enterprise. Agriculture has been theorized to have become the dominant way of producing food since the Neolithic Revolution . Through early biotechnology, the earliest farmers selected and bred the best-suited crops (e.g., those with

11900-464: The cell and transports one intracellular calcium ion out of the cell. The reversal of this exchanger, triggered by the increase in intracellular sodium, results in an increase in the intracellular calcium concentration that is available to the contractile proteins . The increased calcium concentrations lead to the binding of more calcium to troponin C , which results in increased inotropy . Increased intracellular calcium lengthens phase 4 and phase 0 of

12040-458: The cell membrane-bound, ATPase -dependent Na/K pumps), the specific antidote is antidigoxin (antibody fragments against digoxin, trade names Digibind and Digifab). The mechanism of action for drugs such as Digibind and Digifab, used when adverse events occur with the use of digoxin, is that the FAB regions on the antibodies created against digoxin expedite the excretion of the drug into urine. Therefore,

12180-445: The chemical library. It is 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. 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

12320-743: The chemical space. The most prominent differences between natural products and compounds in combinatorial chemistry libraries is the number of chiral centers (much higher in natural compounds), structure rigidity (higher in natural compounds) and number of aromatic moieties (higher in combinatorial chemistry libraries). Other chemical differences between these two groups include the nature of heteroatoms (O and N enriched in natural products, and S and halogen atoms more often present in synthetic compounds), as well as level of non-aromatic unsaturation (higher in natural products). As both structure rigidity and chirality are well-established factors in medicinal chemistry known to enhance compounds specificity and efficacy as

12460-420: The chemical structure is critical to avoid the re-discovery of a chemical agent that is already known for its structure and chemical activity. Mass spectrometry is a method in which individual compounds are identified based on their mass/charge ratio, after ionization. Chemical compounds exist in nature as mixtures, so the combination of liquid chromatography and mass spectrometry (LC-MS) is often used to separate

12600-509: The course of their PhD thesis work. Nineteen institutions offer NIGMS supported BTPs. Biotechnology training is also offered at the undergraduate level and in community colleges. But see also: Domingo, José L.; Bordonaba, Jordi Giné (2011). "A literature review on the safety assessment of genetically modified plants" (PDF) . Environment International . 37 (4): 734–742. Bibcode : 2011EnInt..37..734D . doi : 10.1016/j.envint.2011.01.003 . PMID   21296423 . Archived (PDF) from

12740-445: The current decades, significant progress has been done in creating genetically modified organisms (GMOs) that enhance the diversity of applications and economical viability of industrial biotechnology. By using renewable raw materials to produce a variety of chemicals and fuels, industrial biotechnology is actively advancing towards lowering greenhouse gas emissions and moving away from a petrochemical-based economy. Synthetic biology

12880-488: The difference between beneficial biotechnology (e.g., bioremediation is to clean up an oil spill or hazard chemical leak) versus the adverse effects stemming from biotechnological enterprises (e.g., flow of genetic material from transgenic organisms into wild strains) can be seen as applications and implications, respectively. Cleaning up environmental wastes is an example of an application of environmental biotechnology ; whereas loss of biodiversity or loss of containment of

13020-458: The discovery and manufacturing of traditional small molecule pharmaceutical drugs as well as drugs that are the product of biotechnology – biopharmaceutics . Modern biotechnology can be used to manufacture existing medicines relatively easily and cheaply. The first genetically engineered products were medicines designed to treat human diseases. To cite one example, in 1978 Genentech developed synthetic humanized insulin by joining its gene with

13160-411: The drug candidate based on its safety, specificity of effect, and efficacy of doses. Biotechnology Biotechnology is a multidisciplinary field that involves the integration of natural sciences and engineering sciences in order to achieve the application of organisms and parts thereof for products and services. The term biotechnology was first used by Károly Ereky in 1919 to refer to

13300-467: The drug development process. One example of successful use of this strategy is the screening for antitumor agents by the National Cancer Institute , which started in the 1960s. Paclitaxel was identified from Pacific yew tree Taxus brevifolia . Paclitaxel showed anti-tumour activity by a previously undescribed mechanism (stabilization of microtubules) and is now approved for clinical use for

13440-402: The early 2000s, BioFETs such as the DNA field-effect transistor (DNAFET), gene-modified FET (GenFET) and cell-potential BioFET (CPFET) had been developed. A factor influencing the biotechnology sector's success is improved intellectual property rights legislation—and enforcement—worldwide, as well as strengthened demand for medical and pharmaceutical products. Rising demand for biofuels

13580-631: The evidence for the harm and lack of substantial equivalency of studied GMOs. We emphasize that with over 1783 published articles on GMOs over the last 10 years it is expected that some of them should have reported undesired differences between GMOs and conventional crops even if no such differences exist in reality. and Digoxin Common side effects include breast enlargement with other side effects generally due to an excessive dose. These side effects may include loss of appetite, nausea, trouble seeing, confusion, and an irregular heartbeat . Greater care

13720-423: The expiration date of September, 2011, are being voluntarily recalled to the consumer level. The tablets are being recalled because they may differ in size and therefore could have more or less of the active ingredient, digoxin. A 2008 study suggested digoxin has beneficial effects not only for the heart, but also in reducing the risk of certain kinds of cancer. However, comments on this study suggested that digoxin

13860-607: The fact these organisms are subject to intellectual property law. Biotechnology has several applications in the realm of food security. Crops like Golden rice are engineered to have higher nutritional content, and there is potential for food products with longer shelf lives. Though not a form of agricultural biotechnology, vaccines can help prevent diseases found in animal agriculture. Additionally, agricultural biotechnology can expedite breeding processes in order to yield faster results and provide greater quantities of food. Transgenic biofortification in cereals has been considered as

14000-468: The first biosensor in 1962. Biosensor MOSFETs were later developed, and they have since been widely used to measure physical , chemical , biological and environmental parameters. The first BioFET was the ion-sensitive field-effect transistor (ISFET), invented by Piet Bergveld in 1970. It is a special type of MOSFET, where the metal gate is replaced by an ion -sensitive membrane , electrolyte solution and reference electrode . The ISFET

14140-416: The first forms of biotechnology. These processes also were included in early fermentation of beer . These processes were introduced in early Mesopotamia , Egypt , China and India , and still use the same basic biological methods. In brewing , malted grains (containing enzymes ) convert starch from grains into sugar and then adding specific yeasts to produce beer. In this process, carbohydrates in

14280-409: The first immunosuppressant ( azathioprine ) that allowed human organ transplantation; the first drug to induce remission of childhood leukemia; pivotal anti-cancer treatments; an anti-malarial; an anti-bacterial; and a treatment for gout. Cloning of human proteins made possible the screening of large libraries of compounds against specific targets thought to be linked to specific diseases. This approach

14420-557: The first time that sugar moieties other than ribose and deoxyribose can yield bioactive nucleoside structures. It took until 2004 when the first marine-derived drug was approved. For example, the cone snail toxin ziconotide , also known as Prialt treats severe neuropathic pain. Several other marine-derived agents are now in clinical trials for indications such as cancer, anti-inflammatory use and pain. One class of these agents are bryostatin -like compounds, under investigation as anti-cancer therapy. As above mentioned, combinatorial chemistry

14560-416: The grains broke down into alcohols, such as ethanol. Later, other cultures produced the process of lactic acid fermentation , which produced other preserved foods, such as soy sauce . Fermentation was also used in this time period to produce leavened bread . Although the process of fermentation was not fully understood until Louis Pasteur 's work in 1857, it is still the first use of biotechnology to convert

14700-601: The half-life is considerably longer, along with decrease in Vd (volume of distribution), calling for a reduction in dose or a switch to a different glycoside , such as digitoxin (not available in the United States), which has a much longer elimination half-life of around seven days and is eliminated by the liver. Effective plasma levels vary depending on the medical indication. For congestive heart failure , levels between 0.5 and 1.0 ng/mL are recommended. This recommendation

14840-478: The highest yields) to produce enough food to support a growing population. As crops and fields became increasingly large and difficult to maintain, it was discovered that specific organisms and their by-products could effectively fertilize , restore nitrogen , and control pests . Throughout the history of agriculture, farmers have inadvertently altered the genetics of their crops through introducing them to new environments and breeding them with other plants — one of

14980-474: The identification of screening hits, medicinal chemistry , and optimization of those hits to increase the affinity , selectivity (to reduce the potential of side effects), efficacy/ potency , metabolic stability (to increase the half-life ), and oral bioavailability . Once a compound that fulfills all of these requirements has been identified, the process of drug development can continue. If successful, clinical trials are developed. Modern drug discovery

15120-478: The increased mortality in patients taking digoxin was due to their having worse heart disease than those not taking it. Cardiac arrhythmias may also occur when patients are prescribed digoxin alongside thiazides and loop diuretics. Digitalis (i.e. extracts, including digoxin, from the plant genus Digitalis ) was the first drug used to treat dropsy (swollen ankles—a symptom of heart failure) following its discovery by William Withering . Alongside diuretics , it

15260-430: The individual chemicals. Databases of mass spectra for known compounds are available and can be used to assign a structure to an unknown mass spectrum. Nuclear magnetic resonance spectroscopy is the primary technique for determining chemical structures of natural products. NMR yields information about individual hydrogen and carbon atoms in the structure, allowing detailed reconstruction of the molecule's architecture. When

15400-518: The isolated compound was involved in pain and fever management. They also play an active role in the suppression of cell proliferation. They have the ability to induce death in lymphoblastic leukemia and other human cancer cells. One of the most common drugs derived from salicylates is aspirin , also known as acetylsalicylic acid, with anti-inflammatory and anti-pyretic properties. Some drugs used in modern medicine have been discovered in animals or are based on compounds found in animals. For example,

15540-744: The low consumption of drug and the low cost compared to tests such as Caco-2, gastrointestinal tract (GIT) and Blood–brain barrier (BBB) with which there is a high correlation. A range of parameters can be used to assess the quality of a compound, or a series of compounds, as proposed in the Lipinski's Rule of Five . Such parameters include calculated properties such as cLogP to estimate lipophilicity, molecular weight , polar surface area and measured properties, such as potency, in-vitro measurement of enzymatic clearance etc. Some descriptors such as ligand efficiency (LE) and lipophilic efficiency (LiPE) combine such parameters to assess druglikeness . While HTS

15680-496: The main source of antimicrobial drugs. Streptomyces isolates have been such a valuable source of antibiotics, that they have been called medicinal molds. The classic example of an antibiotic discovered as a defense mechanism against another microbe is penicillin in bacterial cultures contaminated by Penicillium fungi in 1928. Marine environments are potential sources for new bioactive agents. Arabinose nucleosides discovered from marine invertebrates in 1950s, demonstrated for

15820-669: The market, but in 2015 the FDA approved the first GM salmon for commercial production and consumption. There is a scientific consensus that currently available food derived from GM crops poses no greater risk to human health than conventional food, but that each GM food needs to be tested on a case-by-case basis before introduction. Nonetheless, members of the public are much less likely than scientists to perceive GM foods as safe. The legal and regulatory status of GM foods varies by country, with some nations banning or restricting them, and others permitting them with widely differing degrees of regulation. GM crops also provide

15960-810: The methods of genetic engineering . These techniques have allowed for the introduction of new crop traits as well as a far greater control over a food's genetic structure than previously afforded by methods such as selective breeding and mutation breeding . Commercial sale of genetically modified foods began in 1994, when Calgene first marketed its Flavr Savr delayed ripening tomato. To date most genetic modification of foods have primarily focused on cash crops in high demand by farmers such as soybean , corn , canola , and cotton seed oil . These have been engineered for resistance to pathogens and herbicides and better nutrient profiles. GM livestock have also been experimentally developed; in November 2013 none were available on

16100-531: The new technology in 1972 by transferring genetic material into a bacterium, such that the imported material would be reproduced. The commercial viability of a biotechnology industry was significantly expanded on June 16, 1980, when the United States Supreme Court ruled that a genetically modified microorganism could be patented in the case of Diamond v. Chakrabarty . Indian-born Ananda Chakrabarty , working for General Electric , had modified

16240-443: The numbers were higher. Natural products may be useful as a source of novel chemical structures for modern techniques of development of antibacterial therapies. Many secondary metabolites produced by plants have potential therapeutic medicinal properties. These secondary metabolites contain, bind to, and modify the function of proteins (receptors, enzymes, etc.). Consequently, plant derived natural products have often been used as

16380-404: The original on October 9, 2022. In spite of this, the number of studies specifically focused on safety assessment of GM plants is still limited. However, it is important to remark that for the first time, a certain equilibrium in the number of research groups suggesting, on the basis of their studies, that a number of varieties of GM products (mainly maize and soybeans) are as safe and nutritious as

16520-555: The plant (e.g. roots, leaves, and flowers) are crucial for correctly identifying bioactive and pharmacological plant properties. Identifying new drugs and getting them approved for market has proved to be a stringent process due to regulations set by national drug regulatory agencies . Jasmonates are important in responses to injury and intracellular signals. They induce apoptosis and protein cascade via proteinase inhibitor , have defense functions, and regulate plant responses to different biotic and abiotic stresses . Jasmonates also have

16660-457: The production of a chemical known as 1,4-butanediol , which is used in fiber manufacturing. In order to produce 1,4-butanediol, the authors alter the metabolic regulation of the Escherichia coli by CRISPR to induce point mutation in the glt A gene, knockout of the sad gene, and knock-in six genes ( cat 1, suc D, 4hbd , cat 2, bld , and bdh ). Whereas CRISPRi system used to knockdown

16800-460: The production of crops and livestock to use them for food. In selective breeding, organisms with desirable characteristics are mated to produce offspring with the same characteristics. For example, this technique was used with corn to produce the largest and sweetest crops. In the early twentieth century scientists gained a greater understanding of microbiology and explored ways of manufacturing specific products. In 1917, Chaim Weizmann first used

16940-438: The production of products from raw materials with the aid of living organisms. The core principle of biotechnology involves harnessing biological systems and organisms, such as bacteria, yeast , and plants, to perform specific tasks or produce valuable substances. Biotechnology had a significant impact on many areas of society, from medicine to agriculture to environmental science . One of the key techniques used in biotechnology

17080-441: The products). The utilization of biological processes, organisms or systems to produce products that are anticipated to improve human lives is termed biotechnology. By contrast, bioengineering is generally thought of as a related field that more heavily emphasizes higher systems approaches (not necessarily the altering or using of biological materials directly ) for interfacing with and utilizing living things. Bioengineering

17220-422: The purpose of sustainable operations (for the return from bottomless initial investment on R & D) and gaining durable patents rights (for exclusives rights for sales, and prior to this to receive national and international approval from the results on animal experiment and human experiment, especially on the pharmaceutical branch of biotechnology to prevent any undetected side-effects or safety concerns by using

17360-467: The regulation of GMOs between countries, with some of the most marked differences occurring between the US and Europe. Regulation varies in a given country depending on the intended use of the products of the genetic engineering. For example, a crop not intended for food use is generally not reviewed by authorities responsible for food safety. The European Union differentiates between approval for cultivation within

17500-404: The respective conventional non-GM plant, and those raising still serious concerns, was observed. Moreover, it is worth mentioning that most of the studies demonstrating that GM foods are as nutritional and safe as those obtained by conventional breeding, have been performed by biotechnology companies or associates, which are also responsible of commercializing these GM plants. Anyhow, this represents

17640-519: The risk of death in women by 23%. There was no difference in the death rate for men in the study. Digoxin is also used as a standard control substance to test for P-glycoprotein inhibition. Digoxin appears to be a peripherally selective drug due to limited brain uptake caused by binding to P-glycoprotein. The bacteria Eggerthella lenta has been linked to a decrease in the toxicity of Digoxin. These effects have been studied through comparisons of North Americans and Southern Indians, in which

17780-503: The starting point for drug discovery. Until the Renaissance , the vast majority of drugs in Western medicine were plant-derived extracts. This has resulted in a pool of information about the potential of plant species as important sources of starting materials for drug discovery. Botanical knowledge about different metabolites and hormones that are produced in different anatomical parts of

17920-498: The study of the general use of plants in society, and ethnopharmacology , an area inside ethnobotany, which is focused specifically on medicinal uses. Artemisinin , an antimalarial agent from sweet wormtree Artemisia annua , used in Chinese medicine since 200BC is one drug used as part of combination therapy for multiresistant Plasmodium falciparum . Additionally, since machine learning has become more advanced, virtual screening

18060-497: The synthesis of many of the natural products isolated from biological sources. Historically, substances, whether crude extracts or purified chemicals, were screened for biological activity without knowledge of the biological target . Only after an active substance was identified was an effort made to identify the target. This approach is known as classical pharmacology , forward pharmacology, or phenotypic drug discovery. Later, small molecules were synthesized to specifically target

18200-469: The target protein with weaker binding affinity than hits that are identified from HTS. Further modifications through organic synthesis into lead compounds are often required. Such modifications are often guided by protein X-ray crystallography of the protein-fragment complex. The advantages of these approaches are that they allow more efficient screening and the compound library, although small, typically covers

18340-534: The three competing genes ( gab D, ybg C, and tes B) that affect the biosynthesis pathway of 1,4-butanediol. Consequently, the yield of 1,4-butanediol significantly increased from 0.9 to 1.8 g/L. Environmental biotechnology includes various disciplines that play an essential role in reducing environmental waste and providing environmentally safe processes, such as biofiltration and biodegradation . The environment can be affected by biotechnologies, both positively and adversely. Vallero and others have argued that

18480-542: The time, testing is used to find changes that are associated with inherited disorders. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person's chance of developing or passing on a genetic disorder . As of 2011 several hundred genetic tests were in use. Since genetic testing may open up ethical or psychological problems, genetic testing is often accompanied by genetic counseling . Genetically modified crops ("GM crops", or "biotech crops") are plants used in agriculture ,

18620-565: The total company value of pharmaceutical biotech companies worldwide were active in Oncology with Neurology and Rare Diseases being the other two big applications. Pharmacogenomics (a combination of pharmacology and genomics ) is the technology that analyses how genetic makeup affects an individual's response to drugs. Researchers in the field investigate the influence of genetic variation on drug responses in patients by correlating gene expression or single-nucleotide polymorphisms with

18760-802: The treatment of lung, breast, and ovarian cancer, as well as for Kaposi's sarcoma . Early in the 21st century, Cabazitaxel (made by Sanofi , a French firm), another relative of taxol has been shown effective against prostate cancer , also because it works by preventing the formation of microtubules, which pull the chromosomes apart in dividing cells (such as cancer cells). Other examples are: 1. Camptotheca ( Camptothecin · Topotecan · Irinotecan · Rubitecan · Belotecan ); 2. Podophyllum ( Etoposide · Teniposide ); 3a. Anthracyclines ( Aclarubicin · Daunorubicin · Doxorubicin · Epirubicin · Idarubicin · Amrubicin · Pirarubicin · Valrubicin · Zorubicin ); 3b. Anthracenediones ( Mitoxantrone · Pixantrone ). The second main approach involves ethnobotany ,

18900-507: The world's crop lands were planted with GM crops in 2010. As of 2011, 11 different transgenic crops were grown commercially on 395 million acres (160 million hectares) in 29 countries such as the US, Brazil , Argentina , India , Canada, China, Paraguay, Pakistan, South Africa, Uruguay, Bolivia, Australia, Philippines, Myanmar, Burkina Faso, Mexico and Spain. Genetically modified foods are foods produced from organisms that have had specific changes introduced into their DNA with

19040-413: Was Sir David Jack at Allen and Hanbury's, later Glaxo , who pioneered the first inhaled selective beta2-adrenergic agonist for asthma, the first inhaled steroid for asthma, ranitidine as a successor to cimetidine, and supported the development of the triptans. Gertrude Elion, working mostly with a group of fewer than 50 people on purine analogues, contributed to the discovery of the first anti-viral;

19180-559: Was a key technology enabling the efficient generation of large screening libraries for the needs of high-throughput screening. However, now, after two decades of combinatorial chemistry, it has been pointed out that despite the increased efficiency in chemical synthesis, no increase in lead or drug candidates has been reached. This has led to analysis of chemical characteristics of combinatorial chemistry products, compared to existing drugs or natural products. The chemoinformatics concept chemical diversity, depicted as distribution of compounds in

19320-612: Was announced two weeks later. On March 31, 2009, the FDA announced another generic digoxin pill recall by posting this company press release on the agency's web site: "Caraco Pharmaceutical Laboratories, Ltd. Announces a Nationwide Voluntary Recall of All Lots of Digoxin Tablets Due to Size Variability". A March 31 press release from Caraco , a generic pharmaceutical company, stated: [All] tablets of Caraco brand Digoxin, USP, 0.125 mg, and Digoxin, USP, 0.25 mg, distributed prior to March 31, 2009, which are not expired and are within

19460-469: Was distinguishable from other glucosides by the olive-green colored solution produced from this reaction, completely free of red. Charles Cullen admitted in 2003 to killing as many as 40 hospital patients with overdoses of heart medication—usually digoxin—at hospitals in New Jersey and Pennsylvania over his 19-year career as a nurse. On March 10, 2006, he was sentenced to 18 consecutive life sentences and

19600-564: Was the mainstay of treatment for heart failure for over a century. Since the introduction of other drugs with better outcomes and fewer adverse effects, it is generally now only used where heart failure is associated with atrial fibrillation and or a rapid ventricular rate. In certain circumstances it may be used under specialist guidance in addition to, or instead of, the recommended first-line treatments of ACE inhibitor , beta blocker , mineralocorticoid antagonist , and SGLT-2 inhibitor , where they are not effective or not tolerated. Digoxin

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