|
R7 (drug)
R7 is a small-molecule flavonoid and orally active, potent, and selective agonist of the tropomyosin receptor kinase B (TrkB) – the main signaling receptor for the neurotrophin brain-derived neurotrophic factor (BDNF) – which is under development for the treatment of Alzheimer's disease. It is a structural modification and prodrug of tropoflavin (7,8-DHF) with improved potency and pharmacokinetics, namely oral bioavailability and duration. R7 was synthesized by the same researchers who were involved in the discovery of tropoflavin. A patent was filed for R7 in 2013 and was published in 2015. In 2016, it was reported to be in the preclinical stage of development. R7 was superseded by R13 because while R7 had a good drug profile in animals, it showed almost no conversion into tropoflavin in human liver microsomes. In 2010, tropoflavin, a naturally occurring flavonoid, was found to act as an agonist of the TrkB with nanomolar affinity (Kd ≈ 320 nM). Subsequen ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oral Administration
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are intended to have a systemic effect, reaching different parts of the body via the bloodstream, for example. Oral administration can be easier and less painful than other routes, such as injection. However, the onset of action is relatively low, and the effectiveness is reduced if it is not absorbed properly in the digestive system, or if it is broken down by digestive enzymes before it can reach the bloodstream. Some medications may cause gastrointestinal side effects, such as nausea or vomiting, when taken orally. Oral administration can also only be applied to conscious patients, and patients willing and able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mouth ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mouth
In animal anatomy, the mouth, also known as the oral cavity, or in Latin cavum oris, is the opening through which many animals take in food and issue vocal sounds. It is also the cavity lying at the upper end of the alimentary canal, bounded on the outside by the lips and inside by the pharynx. In tetrapods, it contains the tongue and, except for some like birds, teeth. This cavity is also known as the buccal cavity, from the Latin ''bucca'' ("cheek"). Some animal phyla, including arthropods, molluscs and chordates, have a complete digestive system, with a mouth at one end and an anus at the other. Which end forms first in ontogeny is a criterion used to classify bilaterian animals into protostomes and deuterostomes. Development In the first multicellular animals, there was probably no mouth or gut and food particles were engulfed by the cells on the exterior surface by a process known as endocytosis. The particles became enclosed in vacuoles into which enzymes were secr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Animal Model
An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of harming a human. Although biological activity in an animal model does not ensure an effect in humans, many drugs, treatments and cures for human diseases are developed in part with the guidance of animal models. Animal models representing specific taxonomic groups in the research and study of developmental processes are also referred to as model organisms. There are three main types of animal models: Homologous, Isomorphic and Predictive. Homologous animals have the same causes, symptoms and treatment options as would humans who have the same disease. Isomorphic animals share the same symptoms and treatments, only. Predictive models are similar to a particular human disease in only a couple of aspects. However, these are useful in isolating ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Efficacy
Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a pragmatic clinical trial#Efficacy versus effectiveness, distinction is now often made between efficacy and effectiveness. The word ''efficacy'' is used in pharmacology and medicine to refer both to the maximum response achievable from a pharmaceutical drug in research settings, and to the capacity for sufficient therapeutic effect or beneficial change in clinical settings. Pharmacology In pharmacology, efficacy () is the maximum response achievable from an applied or dosed agent, for instance, a small molecule drug. Intrinsic activity is a relative term for a drug's efficacy relative to a drug with the highest observed efficacy. It is a purely descriptive term that has little or no mechanistic interpretation. In order for a drug to have an effect, it needs to bind to its t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Affinity (pharmacology)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion, or protein which binds to the DNA double helix. The relationship between ligand and binding partner is a function of charge, hydrophobicity, and molecular structure. Binding occurs by intermolecular forces, such as ionic bonds, hydrogen bonds and Van der Waals forces. The association or docking is actually reversible through dissociation. Measurably irreversible covalent bonding between a ligand and target molecule is atypical in biological systems. In contrast to the definition of liga ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nanomolar
Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of solution. In chemistry, the most commonly used unit for molarity is the number of moles per liter, having the unit symbol mol/L or mol/ dm3 in SI unit. A solution with a concentration of 1 mol/L is said to be 1 molar, commonly designated as 1 M. Definition Molar concentration or molarity is most commonly expressed in units of moles of solute per litre of solution. For use in broader applications, it is defined as amount of substance of solute per unit volume of solution, or per unit volume available to the species, represented by lowercase c: :c = \frac = \frac = \frac. Here, n is the amount of the solute in moles, N is the number of constituent particles present in volume V (in litres) of the solution, and N_\text is the Avo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Natural Product
A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical synthesis (both semisynthesis and total synthesis) and have played a central role in the development of the field of organic chemistry by providing challenging synthetic targets. The term natural product has also been extended for commercial purposes to refer to cosmetics, dietary supplements, and foods produced from natural sources without added artificial ingredients. Within the field of organic chemistry, the definition of natural products is usually restricted to organic compounds isolated from natural sources that are produced by the pathways of primary or secondary metabolism. Within the field of medicinal chemistry, the definition is often further restricted to secondary metabolites. Secondary metabolites (or specialized metabolites ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Microsome
In cell biology, microsomes are heterogeneous vesicle-like artifacts (~20-200 nm diameter) re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, living cells. Rough (containing ribosomes) and smooth (without ribosomes) microsomes are made from the endoplasmic reticulum through cell disruption. These microsomes have an inside that is exactly the same as the endoplasmic reticulum lumen. Both forms of microsomes can be purified by a process known as equilibrium density centrifugation. Rough and smooth microsomes do differ in their proteins and rough microsomes have shown occurrence of translation and translocation at the same time besides certain exceptions from proteins in yeast. Signal Hypothesis Microsomes play a role in the signal hypothesis. This hypothesis explores in vitro protein translation for a mRNA encoding secretory protein. When microsomes are present, the proteins sh ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it is located in the quadrant (anatomy), right upper quadrant of the abdomen, below the thoracic diaphragm, diaphragm. Its other roles in metabolism include the regulation of Glycogen, glycogen storage, decomposition of red blood cells, and the production of hormones. The liver is an accessory digestive organ that produces bile, an alkaline fluid containing cholesterol and bile acids, which helps the fatty acid degradation, breakdown of fat. The gallbladder, a small pouch that sits just under the liver, stores bile produced by the liver which is later moved to the small intestine to complete digestion. The liver's highly specialized biological tissue, tissue, consisting mostly of hepatocytes, regulates a w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
R13 (drug)
R13 is a small-molecule flavonoid and orally active, potent, and selective agonist of the tropomyosin receptor kinase B (TrkB) – the main signaling receptor for the neurotrophin brain-derived neurotrophic factor (BDNF) – which is under development for the potential treatment of Alzheimer's disease. It is a structural modification and prodrug of tropoflavin (7,8-DHF) with improved potency and pharmacokinetics, namely oral bioavailability and duration. The compound is a replacement for the earlier tropoflavin prodrug R7 and has similar properties to it. It was developed because while R7 displayed a good drug profile in animal studies, it showed almost no conversion into tropoflavin in human liver microsomes. In contrast to R7, R13 is readily hydrolyzed into tropoflavin in human liver microsomes. See also * List of investigational antidepressants This is a list of investigational antidepressants, or antidepressants that are currently under development for clinical ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Preclinical Development
In drug development, preclinical development, also termed preclinical studies or nonclinical studies, is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and drug safety data are collected, typically in laboratory animals. The main goals of preclinical studies are to determine a starting, safe dose for first-in-human study and assess potential toxicity of the product, which typically include new medical devices, prescription drugs, and diagnostics. Companies use stylized statistics to illustrate the risks in preclinical research, such as that on average, only one in every 5,000 compounds that enters drug discovery to the stage of preclinical development becomes an approved drug. Types of preclinical research Each class of product may undergo different types of preclinical research. For instance, drugs may undergo pharmacodynamics (what the drug does to the body) (PD), pharmacokinetics (wha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Patent
A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A patent is not the grant of a right to make or use or sell. It does not, directly or indirectly, imply any such right. It grants only the right to exclude others. The supposition that a right to make is created by the patent grant is obviously inconsistent with the established distinctions between generic and specific patents, and with the well-known fact that a very considerable portion of the patents granted are in a field covered by a former relatively generic or basic patent, are tributary to such earlier patent, and cannot be practiced unless by license thereunder." – ''Herman v. Youngstown Car Mfg. Co.'', 191 F. 579, 584–85, 112 CCA 185 (6th Cir. 1911) In most countries, patent rights fall under private law and the patent holder mus ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
