Action inhibitors

Cancer Elevated levels of AEA in glioblastomas, increased levels of 2-AG in meningiomas, elevated levels of both AEA and 2-AG in colorectal carcinoma, with possible anti-tumour action Inhibitors of degradation (both FAAH and cellular re-uptake)... 

Inhibitors of the catalytic activities of enzymes provide both pharmacologic agents and research tools for study of the mechanism of enzyme action. Inhibitors can be classified based upon their site of action on the enzyme, on whether or not they chemically modify the enzyme, or on the kinetic parameters they influence. KineticaUy, we distinguish two classes of inhibitors based upon whether raising the substrate concentration does or does not overcome the inhibition. 

Adnane L, Trail PA, Taylor I, Wilhelm SM. Sorafenib (BAY 43-9006, Nexavar((R))), a dual-action inhibitor that targets RAF/ MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/ PDGFR in tumor vasculature. Meth.Enzymol. 2005 407 597-612. 

Addition of a low-molecular-weight substrate to the equilibrium mixture formed from equimolar amounts of SLPI and HLE resulted in time-dependent release of product, indicating that enzyme, inhibitor, substrate and their complexes were in true equilibrium [51]. Incubation of rSLPI-HLE complex with a,-PI resulted in dissociation of rSLPI and formation of an a,-PI-HLE complex. The fact that the dissociated rSLPI retained its ability to inhibit HLE is further indication that it may be a standard mechanism of action inhibitor [82]. In vivo, intratracheally instilled rSLPI is capable of significantly protecting against HLE-induced emphysema in the hamster (EMP model) for pretreatment times of up to 8 h [82]. 

Bacterial infections are treated with antibiotics. There are many antibiotics available, but they fall into three major groups based on their mode of action inhibitors of bacterial nucleic acid synthesis inhibitors of cell wall synthesis and inhibition of bacterial protein synthesis. Resistance of bacteria to commonly-used antibiotics has become a major problem necessitating the development of new antibiotics. Tuberculosis infection is difficult to treat and requires a combination of at least three different antibiotics. 

Frye, L.L., K.P. Cusack, and D.A. Leonard (1993). 32-MethyI-32-oxylanosteroIs Dual-action inhibitors of cholesterol biosynthesis. J. Med. Chem. 36, 410-416. 

Mechanism of action Inhibitors of catechol-O-methyltransferase (COMT), the enzyme that converts levodopa to 3-O-methyldopa (30MD). Increased plasma levels of 30MD are associated with poor response to levodopa, partly because the compound competes with levodopa for active transport into the CNS. 

Intensive use of the herbicide paraquat has resulted in the evolution of resistance in various weed species. Intensive research on the resistance mechanisms was mainly carried out with resistant biotypes from Hordeum spp. and Conyza spp., and altered distribution of the herbicide in the resistant weeds was suggested as the cause - or at least the partial cause - of resistance. In resistant Conyza canadensis it was supposed that a paraquat inducible protein may function by carrying paraquat to a metabolically inactive compartment, either the cell wall or the vacuole. This sequestration process would prevent the herbicide from getting in sufficient amounts into the chloroplasts as the cellular site of paraquat action. Inhibitors of membrane transport systems, e.g., N,N-dicyclohexylcarbodii-mide (DCCD), caused a delay in the recovery of photosynthetic functions of the paraquat-resistant biotype, when given after the herbicide. These transport inhibitor experiments supported the involvement of a membrane transporter in paraquat resistance [75]. 

Giridhar, R Indu, E.R Vinod, K Chandrashekar, A. Ravishankar, G.A. CasteUanos-Hernandez, O.A. (2004). Direct somatic embryogenesis from Coffea arabica L. and Coffea canephora P. ex Fr. under the influence of ethylene action inhibitor-silver nitrate. Acta Physiologiae Plantarum, Vol.26, No.3, (September 2004), p>p. 299-305, ISSN 1861-1664... 

Corrosion suppression by inhibitors can be achieved by adding chemical species to tlie environment, which lead to a strong reduction of tlie dissolution rate. Depending on tlieir specific action, corrosion inliibitors can be divided into tlie following groups. 

Enzyme action is frequently accelerated or retarded by the presence of other substances both organic and inorganic. Such substances have been divided into three categories (a) co-enzymes, without which certain enzymes are unable to function (i) activators, and (c) inhibitors. 

Bronze disease necessitates immediate action to halt the process and remove the cause. For a long time, stabilization was sought by removal of the cuprous chloride by immersing the object in a solution of sodium sesquicarbonate. This process was, however, extremely time-consuming, frequentiy unsuccesshil, and often the cause of unpleasant discolorations of the patina. Objects affected by bronze disease are mostiy treated by immersion in, or surface appHcation of, 1 H-henzotriazole [95-14-7] C H N, a corrosion inhibitor for copper. A localized treatment is the excavation of cuprous chloride from the affected area until bare metal is obtained, followed by appHcation of moist, freshly precipitated silver oxide which serves to stabilize the chloride by formation of silver chloride. Subsequent storage in very dry conditions is generally recommended to prevent recurrence. 

The question as to whether a flame retardant operates mainly by a condensed-phase mechanism or mainly by a vapor-phase mechanism is especially comphcated in the case of the haloalkyl phosphoms esters. A number of these compounds can volatilize undecomposed or undergo some thermal degradation to release volatile halogenated hydrocarbons (37). The intact compounds or these halogenated hydrocarbons are plausible flame inhibitors. At the same time, thek phosphoms content may remain at least in part as relatively nonvolatile phosphoms acids which are plausible condensed-phase flame retardants (38). There is no evidence for the occasionally postulated formation of phosphoms haUdes. Some evidence has been presented that the endothermic vaporization and heat capacity of the intact chloroalkyl phosphates may be a main part of thek action (39,40). 

He/minthosporium (15). The mode of action is considered to be inhibition of the enzyme NADPH-cytochrome C reductase, which results in the generation of free radicals and/or peroxide derivatives of flavin which oxidize adjacent unsaturated fatty acids to dismpt membrane integrity (16) (see Enzyme inhibitors). 

Corrosion Inhibitors. The corrosion inhibitors used in diesel fuel ate generally similar to those used in gasoline and, like the latter, produce an effect primarily by surface action. If amine additives ate used for detergency, these may provide some corrosion protection as well. 

Biorational approaches have proven useful in the development of classes of herbicides which inhibit essential metaboHc pathways common to all plants and thus are specific to plants and have low toxicity to mammalian species. Biorational herbicide development remains a high risk endeavor since promising high activities observed in the laboratory may be nullified by factors such as limitations in plant uptake and translocation, and the instabiHty or inactivity of biochemical en2yme inhibitors under the harsher environmental conditions in the field. Despite these recogni2ed drawbacks, biorational design of herbicides has shown sufficient potential to make the study of herbicide modes of action an important and growing research area. 

Bleaching Herbicides. Membrane-based modes of herbicidal action relevant to photosynthesis (37) include those of inhibitors of carotenoid biosynthesis, eg, norflura2on, diftmon, y -phenoxyben2amines inhibitors of chlorophyll biosynthesis, eg, oxadia2on, DTP or... 

A second class of herbicides primarily affects ( -carotene desaturase. These herbicides are apparent feedback inhibitors of PD as well. This class of compounds includes dihydropyrones like LS 80707 [90936-96-2] (56) and 6-methylpyridines (57,58). The third class consists of the ben2oylcyclohexane-diones, eg, 2-(4-chloro-2-nitroben2oyl)-5,5-dimethyl-cyclohexane-I,3-dione. This class of atypical bleaching herbicides induces phytoene accumulation when appHed either pre- or post-emergence. However, it does not inhibit phytoene desaturase activity in vitro (59). Amitrole also has been considered a bleaching herbicide, though its main mode of action is inhibition of amino acid synthesis. 

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