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Chemogenomics
Chemogenomics, or chemical genomics, is the systematic screening of targeted chemical libraries of small molecules against individual drug target families (e.g., GPCRs, nuclear receptors, kinases, proteases, etc.) with the ultimate goal of identification of novel drugs and drug targets. Typically some members of a target library have been well characterized where both the function has been determined and compounds that modulate the function of those targets ( ligands in the case of receptors, inhibitors of enzymes, or blockers of ion channels) have been identified. Other members of the target family may have unknown function with no known ligands and hence are classified as orphan receptors. By identifying screening hits that modulate the activity of the less well characterized members of the target family, the function of these novel targets can be elucidated. Furthermore, the hits for these targets can be used as a starting point for drug discovery. The completion of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chemical Genomics Robot
A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., without breaking chemical bonds. Chemical substances can be simple substances (substances consisting of a single chemical element), chemical compounds, or alloys. Chemical substances are often called 'pure' to set them apart from mixtures. A common example of a chemical substance is pure water; it has the same properties and the same ratio of hydrogen to oxygen whether it is isolated from a river or made in a laboratory. Other chemical substances commonly encountered in pure form are diamond (carbon), gold, table salt (sodium chloride) and refined sugar (sucrose). However, in practice, no substance is entirely pure, and chemical purity is specified according to the intended use of the chemical. Chemical substances exist as solids, liquids, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Drug Discovery Hit To Lead
Hit to lead (H2L) also known as lead generation is a stage in early drug discovery where small molecule hits from a high throughput screen (HTS) are evaluated and undergo limited optimization to identify promising lead compounds. These lead compounds undergo more extensive optimization in a subsequent step of drug discovery called lead optimization (LO). The drug discovery process generally follows the following path that includes a hit to lead stage: * Target validation (TV) → Assay development → High-throughput screening (HTS) → Hit to lead (H2L) → Lead optimization (LO) → Preclinical development → Clinical development The hit to lead stage starts with confirmation and evaluation of the initial screening hits and is followed by synthesis of analogs (hit expansion). Typically the initial screening hits display binding affinities for their biological target in the micromolar (10−6 molar concentration) range. Through limited H2L optimization, the affinities of the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gram-negative
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall sandwiched between an inner cytoplasmic cell membrane and a bacterial outer membrane. Gram-negative bacteria are found in virtually all environments on Earth that support life. The gram-negative bacteria include the model organism ''Escherichia coli'', as well as many pathogenic bacteria, such as ''Pseudomonas aeruginosa'', '' Chlamydia trachomatis'', and '' Yersinia pestis''. They are a significant medical challenge as their outer membrane protects them from many antibiotics (including penicillin), detergents that would normally damage the inner cell membrane, and lysozyme, an antimicrobial enzyme produced by animals that forms part of the innate immune system. Additionally, the outer leaflet of this membrane comprises a comp ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Muramyl Ligase
The bacterial cell wall provides strength and rigidity to counteract internal osmotic pressure, and protection against the environment. The peptidoglycan layer gives the cell wall its strength, and helps maintain the overall shape of the cell. The basic peptidoglycan structure of both Gram-positive and Gram-negative bacteria comprises a sheet of glycan chains connected by short cross-linking polypeptides. Biosynthesis of peptidoglycan is a multi-step (11-12 steps) process comprising three main stages: # formation of UDP- N-acetylmuramic acid (UDPMurNAc) from N-acetylglucosamine (GlcNAc). # addition of a short polypeptide chain to the UDPMurNAc. # addition of a second GlcNAc to the disaccharide-pentapeptide building block and transport of this unit through the cytoplasmic membrane and incorporation into the growing peptidoglycan layer. Stage two involves four key Mur ubiquitin ligase enzymes: MurCEC, MurDEC, MurEEC and MurFEC. These four Mur ligases are responsible for the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
P-gp
P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells. More formally, it is an ATP-dependent efflux pump with broad substrate specificity. It exists in animals, fungi, and bacteria, and it likely evolved as a defense mechanism against harmful substances. P-gp is extensively distributed and expressed in the intestinal epithelium where it pumps xenobiotics (such as toxins or drugs) back into the intestinal lumen, in liver cells where it pumps them into bile ducts, in the cells of the proximal tubule of the kidney where it pumps them into urinary filtrate (in the proximal tubule), and in the capillary endothelial cells composing the blood–brain barrier and blood–testis barrier, where it pumps them back into the capilla ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PTP1B
Tyrosine-protein phosphatase non-receptor type 1 also known as protein-tyrosine phosphatase 1B (PTP1B) is an enzyme that is the founding member of the protein tyrosine phosphatase (PTP) family. In humans it is encoded by the ''PTPN1'' gene. PTP1B is a negative regulator of the insulin signaling pathway and is considered a promising potential therapeutic target, in particular for treatment of type 2 diabetes. It has also been implicated in the development of breast cancer and has been explored as a potential therapeutic target in that avenue as well. Structure and function PTP1B was first isolated from a human placental protein extract, but it is expressed in many tissues. PTP1B is localized to the cytoplasmic face of the endoplasmic reticulum. PTP1B can dephosphorylate the phosphotyrosine residues of the activated insulin receptor kinase. In mice, genetic ablation of PTPN1 results in enhanced insulin sensitivity. Several other tyrosine kinases, including epidermal growth factor r ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sodium-glucose Transport Proteins
Sodium-dependent glucose cotransporters (or sodium-glucose linked transporter, SGLT) are a family of glucose transporter found in the intestinal mucosa (enterocytes) of the small intestine (SGLT1) and the proximal tubule of the nephron ( SGLT2 in PCT and SGLT1 in PST). They contribute to renal glucose reabsorption. In the kidneys, 100% of the filtered glucose in the glomerulus has to be reabsorbed along the nephron (98% in PCT, via SGLT2). If the plasma glucose concentration is too high (hyperglycemia), glucose passes into the urine ( glucosuria) because SGLT are saturated with the filtered glucose. Types The two most well known members of SGLT family are SGLT1 and SGLT2, which are members of the SLC5A gene family. In addition to SGLT1 and SGLT2, there are 10 other members in the human protein family SLC5A. Of these, SLC5A4/SGLT3 (SAAT1) is a low-affinity transporter for glucose, but seems to have more of an electric function. The other SLC5 proteins transport mannose ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ayurveda
Ayurveda () is an alternative medicine system with historical roots in the Indian subcontinent. The theory and practice of Ayurveda is pseudoscientific. Ayurveda is heavily practiced in India and Nepal, where around 80% of the population report using it. Ayurveda therapies have varied and evolved over more than two millennia. Therapies include herbal medicines, special diets, meditation, yoga, massage, laxatives, enemas, and medical oils. Ayurvedic preparations are typically based on complex herbal compounds, minerals, and metal substances (perhaps under the influence of early Indian alchemy or '' rasashastra''). Ancient Ayurveda texts also taught surgical techniques, including rhinoplasty, kidney stone extractions, sutures, and the extraction of foreign objects. The main classical Ayurveda texts begin with accounts of the transmission of medical knowledge from the gods to sages, and then to human physicians. Printed editions of the '' Sushruta Samhita'' (''Sushruta's ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Traditional Chinese Medicine
Traditional Chinese medicine (TCM) is an alternative medical practice drawn from traditional medicine in China. It has been described as "fraught with pseudoscience", with the majority of its treatments having no logical mechanism of action. Medicine in traditional China encompassed a range of sometimes competing health and healing practices, folk beliefs, literati theory and Confucian philosophy, herbal remedies, food, diet, exercise, medical specializations, and schools of thought. In the early twentieth century, Chinese cultural and political modernizers worked to eliminate traditional practices as backward and unscientific. Traditional practitioners then selected elements of philosophy and practice and organized them into what they called "Chinese medicine" (''Zhongyi''). In the 1950s, the Chinese government sponsored the integration of Chinese and Western medicine, and in the Great Proletarian Cultural Revolution of the 1960s, promoted Chinese medicine as inexpens ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mode Of Action
A mode of action (MoA) describes a functional or anatomical change, resulting from the exposure of a living organism to a substance. In comparison, a mechanism of action (MOA) describes such changes at the molecular level. A mode of action is important in classifying chemicals, as it represents an intermediate level of complexity in between molecular mechanisms and physiological outcomes, especially when the exact molecular target has not yet been elucidated or is subject to debate. A mechanism of action of a chemical could be "binding to DNA" while its broader mode of action would be "transcriptional regulation". However, there is no clear consensus and the term mode of action is also often used, especially in the study of pesticides, to describe molecular mechanisms such as action on specific nuclear receptors or enzymes. Disinfectants are commonly used in order to eliminate microorganisms. The effectiveness of a disinfectant is dependent on both the chemical composition of the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological properties, its behavior, and the products of behavior. An organism's phenotype results from two basic factors: the expression of an organism's genetic code, or its genotype, and the influence of environmental factors. Both factors may interact, further affecting phenotype. When two or more clearly different phenotypes exist in the same population of a species, the species is called polymorphic. A well-documented example of polymorphism is Labrador Retriever coloring; while the coat color depends on many genes, it is clearly seen in the environment as yellow, black, and brown. Richard Dawkins in 1978 and then again in his 1982 book '' The Extended Phenotype'' suggested that one can regard bird nests and other built structures such as ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
