|
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 screening, 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 phase, Lead optimization (LO) → Preclinical development → Drug development#Clinical phase, Clinical development The hit to lead stage starts with confirmation and evaluation of the initial screening hits and is followed by synthesis of structural analog, analogs (hit expansion). Typically the initial screening hits display binding affinity, binding affinities for their biologic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Drug Discovery
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 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 i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
New York Times
''The New York Times'' (''NYT'') is an American daily newspaper based in New York City. ''The New York Times'' covers domestic, national, and international news, and publishes opinion pieces, investigative reports, and reviews. As one of the longest-running newspapers in the United States, the ''Times'' serves as one of the country's Newspaper of record, newspapers of record. , ''The New York Times'' had 9.13 million total and 8.83 million online subscribers, both by significant margins the List of newspapers in the United States, highest numbers for any newspaper in the United States; the total also included 296,330 print subscribers, making the ''Times'' the second-largest newspaper by print circulation in the United States, following ''The Wall Street Journal'', also based in New York City. ''The New York Times'' is published by the New York Times Company; since 1896, the company has been chaired by the Ochs-Sulzberger family, whose current chairman and the paper's publ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Conformational Change
In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors. A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or other factors; each possible shape is called a conformation, and a transition between them is called a ''conformational change''. Factors that may induce such changes include temperature, pH, voltage, light in chromophores, concentration of ions, phosphorylation, or the binding of a ligand. Transitions between these states occur on a variety of length scales (tenths of Å to nm) and time scales (ns to s), and have been linked to functionally relevant phenomena such as allosteric signaling and enzyme catalysis. Laboratory analysis Many biophysical techniques such as crystallography, NMR, electron paramagnetic resonance (EPR) using spin label techniques, circular dichroism (CD), hydrogen exchange, and FRET can be used to study macromo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Stoichiometry
Stoichiometry () is the relationships between the masses of reactants and Product (chemistry), products before, during, and following chemical reactions. Stoichiometry is based on the law of conservation of mass; the total mass of reactants must equal the total mass of products, so the relationship between reactants and products must form a ratio of positive integers. This means that if the amounts of the separate reactants are known, then the amount of the product can be calculated. Conversely, if one reactant has a known quantity and the quantity of the products can be empirically determined, then the amount of the other reactants can also be calculated. This is illustrated in the image here, where the unbalanced equation is: : : However, the current equation is imbalanced. The reactants have 4 hydrogen and 2 oxygen atoms, while the product has 2 hydrogen and 3 oxygen. To balance the hydrogen, a coefficient of 2 is added to the product H2O, and to fix the imbalance of oxygen, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thermodynamics
Thermodynamics is a branch of physics that deals with heat, Work (thermodynamics), work, and temperature, and their relation to energy, entropy, and the physical properties of matter and radiation. The behavior of these quantities is governed by the four laws of thermodynamics, which convey a quantitative description using measurable macroscopic physical quantity, physical quantities but may be explained in terms of microscopic constituents by statistical mechanics. Thermodynamics applies to various topics in science and engineering, especially physical chemistry, biochemistry, chemical engineering, and mechanical engineering, as well as other complex fields such as meteorology. Historically, thermodynamics developed out of a desire to increase the thermodynamic efficiency, efficiency of early steam engines, particularly through the work of French physicist Nicolas Léonard Sadi Carnot, Sadi Carnot (1824) who believed that engine efficiency was the key that could help France win ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Receptor–ligand Kinetics
In biochemistry, receptor–ligand kinetics is a branch of chemical kinetics in which the kinetic species are defined by different non-covalent bindings and/or conformations of the molecules involved, which are denoted as '' receptor(s)'' and '' ligand(s)''. Receptor–ligand binding kinetics also involves the on- and off-rates of binding. A main goal of receptor–ligand kinetics is to determine the concentrations of the various kinetic species (i.e., the states of the receptor and ligand) at all times, from a given set of initial concentrations and a given set of rate constants. In a few cases, an analytical solution of the rate equations may be determined, but this is relatively rare. However, most rate equations can be integrated numerically, or approximately, using the steady-state approximation. A less ambitious goal is to determine the final ''equilibrium'' concentrations of the kinetic species, which is adequate for the interpretation of equilibrium binding data. A con ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dual Polarisation Interferometry
Dual-polarization interferometry (DPI) is an analytical technique that probes molecular layers adsorbed to the surface of a waveguide using the evanescent wave of a laser beam. It is used to measure the conformational change in proteins, or other biomolecules, as they function (referred to as the conformation activity relationship). Instrumentation DPI focuses laser light into two waveguides. One of these functions as the "sensing" waveguide having an exposed surface while the second one functions to maintain a reference beam. A two-dimensional interference pattern is formed in the far field by combining the light passing through the two waveguides. The DPI technique rotates the polarization of the laser, to alternately excite two polarization modes of the waveguides. Measurement of the interferogram for both polarizations allows both the refractive index and the thickness of the adsorbed layer to be calculated. The polarization can be switched rapidly, allowing real-time m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Surface Plasmon Resonance
Surface plasmon resonance (SPR) is a phenomenon that occurs where electrons in a thin metal sheet become excited by light that is directed to the sheet with a particular angle of incidence (optics), angle of incidence, and then travel parallel to the sheet. Assuming a constant light source wavelength and that the metal sheet is thin, the angle of incidence that triggers SPR is related to the refractive index of the material and even a small change in the refractive index will cause SPR to not be observed. This makes SPR a possible technique for detecting particular substances (analytes) and SPR biosensors have been developed to detect various important biomarkers. Explanation The surface plasmon polariton is a non-radiative Surface wave#Electromagnetic waves, electromagnetic surface wave that propagates in a direction parallel to the negative permittivity/dielectric material interface. Since the wave is on the boundary of the conductor and the external medium (air, water or vacuu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dynamic Light Scattering
Dynamic light scattering (DLS) is a technique in physics that can be used to determine the size distribution profile of small particles in suspension or polymers in solution. In the scope of DLS, temporal fluctuations are usually analyzed using the intensity or photon autocorrelation function (also known as photon correlation spectroscopy – PCS or quasi-elastic light scattering – QELS). In the time domain analysis, the autocorrelation function (ACF) usually decays starting from zero delay time, and faster dynamics due to smaller particles lead to faster decorrelation of scattered intensity trace. It has been shown that the intensity ACF is the Fourier transform of the power spectrum, and therefore the DLS measurements can be equally well performed in the spectral domain. DLS can also be used to probe the behavior of complex fluids such as concentrated polymer solutions. Setup A monochromatic light source, usually a laser, is shot through a polarizer and into a sample. The s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Isothermal Titration Calorimetry
In chemical thermodynamics, isothermal titration calorimetry (ITC) is a physical technique used to determine the Conjugate variables (thermodynamics), thermodynamic parameters of interactions in Solution (chemistry), solution. ITC is the only technique capable comprehensively characterizing Thermodynamics, thermodynamic and even Kinetic energy, kinetic profile of the interaction by simultaneously determining binding constants (K_a), reaction stoichiometry (n), enthalpy (\Delta H), Gibbs free energy (\Delta G) and entropy (\Delta S) within a single experiment. It consists of two cells which are enclosed in an adiabatic jacket. The compounds to be studied are placed in the sample cell, while the other cell, the reference cell, is used as a Treatment and control groups, control and contains the Buffer solution, buffer in which the sample is dissolved. The technique quantifies the heat released or absorbed during the binding process by incrementally adding one reactant (via a syringe ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nuclear Magnetic Resonance
Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are disturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with a frequency characteristic of the magnetic field at the nucleus. This process occurs near resonance, when the oscillation frequency matches the intrinsic frequency of the nuclei, which depends on the strength of the static magnetic field, the chemical environment, and the magnetic properties of the isotope involved; in practical applications with static magnetic fields up to ca. 20 tesla, the frequency is similar to VHF and UHF television broadcasts (60–1000 MHz). NMR results from specific magnetic properties of certain atomic nuclei. High-resolution nuclear magnetic resonance spectroscopy is widely used to determine the structure of organic molecules in solution and study molecular physics and crystals as well as non-crysta ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
