In biochemistry, allosteric regulation is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site.
Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it. Drug design frequently but not necessarily relies on computer modeling techniques. This type of modeling is sometimes referred to as computer-aided drug design. Finally, drug design that relies on the knowledge of the three-dimensional structure of the biomolecular target is known as structure-based drug design. In addition to small molecules, biopharmaceuticals including peptides and especially therapeutic antibodies are an increasingly important class of drugs and computational methods for improving the affinity, selectivity, and stability of these protein-based therapeutics have also been developed.
In the field of molecular modeling, docking is a method which predicts the preferred orientation of one molecule to a second when a ligand and a target are bound to each other to form a stable complex. Knowledge of the preferred orientation in turn may be used to predict the strength of association or binding affinity between two molecules using, for example, scoring functions.
(+)-CPCA is a stimulant drug similar in structure to pethidine and to RTI-31, but nocaine is lacking the two-carbon bridge of RTI-31's tropane skeleton. This compound was first developed as a substitute agent for cocaine.
In molecular modelling, docking is a method which predicts the preferred orientation of one molecule to another when bound together in a stable complex. In the case of protein docking, the search space consists of all possible orientations of the protein with respect to the ligand. Flexible docking in addition considers all possible conformations of the protein paired with all possible conformations of the ligand.
Maslinic acid is a compound derived from dry olive-pomace oil which is a byproduct of olive oil extraction. It is a member of the group of triterpenes known as oleananes.
Serine/threonine-protein kinase PAK 4 is an enzyme that in humans is encoded by the PAK4 gene.
Himbacine is an alkaloid isolated from the bark of Australian magnolias. Himbacine has been synthesized using a Diels-Alder reaction as a key step. Himbacine's activity as a muscarinic receptor antagonist, with specificity for the muscarinic acetylcholine receptor M2, made it a promising starting point in Alzheimer's disease research. The development of a muscarinic antagonist based on himbacine failed but an analog, vorapaxar, has been approved by the FDA as a thrombin receptor antagonist.
Inte:Ligand was founded in Maria Enzersdorf, Lower Austria (Niederösterreich) in 2003. They established the company headquarters on Mariahilferstrasse in Vienna, Austria that same year.
MacroModel is a computer program for molecular modelling of organic compounds and biopolymers. It features various chemistry force fields, plus energy minimizing algorithms, to predict geometry and relative conformational energies of molecules. MacroModel is maintained by Schrödinger, LLC.
Bcr-Abl tyrosine-kinase inhibitors (TKI) are the first-line therapy for most patients with chronic myelogenous leukemia (CML). More than 90% of CML cases are caused by a chromosomal abnormality that results in the formation of a so-called Philadelphia chromosome. This abnormality was discovered by Peter Nowell in 1960 and is a consequence of fusion between the Abelson (Abl) tyrosine kinase gene at chromosome 9 and the break point cluster (Bcr) gene at chromosome 22, resulting in a chimeric oncogene (Bcr-Abl) and a constitutively active Bcr-Abl tyrosine kinase that has been implicated in the pathogenesis of CML. Compounds have been developed to selectively inhibit the tyrosine kinase.
c-Met inhibitors are a class of small molecules that inhibit the enzymatic activity of the c-Met tyrosine kinase, the receptor of hepatocyte growth factor/scatter factor (HGF/SF). These inhibitors may have therapeutic application in the treatment of various types of cancers.
MN-25 (UR-12) is a drug invented by Bristol-Myers Squibb, that acts as a reasonably selective agonist of peripheral cannabinoid receptors. It has moderate affinity for CB2 receptors with a Ki of 11 nM, but 22x lower affinity for the psychoactive CB1 receptors with a Ki of 245 nM. The indole 2-methyl derivative has the ratio of affinities reversed however, with a Ki of 8 nM at CB1 and 29 nM at CB2, which contrasts with the usual trend of 2-methyl derivatives having increased selectivity for CB2 (cf. JWH-018 vs JWH-007, JWH-081 vs JWH-098).
Autophosphorylation is a type of post-translational modification of proteins. It is generally defined as the phosphorylation of the kinase by itself. In eukaryotes, this process occurs by the addition of a phosphate group to serine, threonine or tyrosine residues within protein kinases, normally to regulate the catalytic activity. Autophosphorylation may occur when a kinases' own active site catalyzes the phosphorylation reaction, or when another kinase of the same type provides the active site that carries out the chemistry. The latter often occurs when kinase molecules dimerize. In general, the phosphate groups introduced are gamma phosphates from nucleoside triphosphates, most commonly ATP.
The 3C-like protease (3CLpro) or main protease (Mpro), formally known as C30 endopeptidase or 3-chymotrypsin-like protease, is the main protease found in coronaviruses. It cleaves the coronavirus polyprotein at eleven conserved sites. It is a cysteine protease and a member of the PA clan of proteases. It has a cysteine-histidine catalytic dyad at its active site and cleaves a Gln–(Ser/Ala/Gly) peptide bond.
Eudistomins are β-carboline derivatives, isolated from ascidians, like Ritterella sigillinoides, Lissoclinum fragile, or Pseudodistoma aureum.
CGS-13767 is an anxiolytic GABA receptor ligand.
Targeted covalent inhibitors (TCIs) or Targeted covalent drugs are rationally designed inhibitors that bind and then bond to their target proteins. These inhibitors possess a bond-forming functional group of low chemical reactivity that, following binding to the target protein, is positioned to react rapidly with a proximate nucleophilic residue at the target site to form a bond.
Xue-Min Cheng is a medicinal chemist, author and pharmaceutical executive best known as the co-author of The Logic of Chemical Synthesis, which formalized retrosynthesis. The concept for this Elias J. Corey won the 1990 Nobel Prize in Chemistry.
Mozenavir (DMP-450) is an antiviral drug which was developed as a treatment for HIV/AIDS. It acts as an HIV protease inhibitor and binds to this target with high affinity, however despite promising results in early testing, mozenavir was unsuccessful in human clinical trials. Studies continue into related derivatives.
