Inhibitors, multiple

P. Foley, M. Gerlach, M.B.FI. Youdim, P. Riederer, MAO inhibitors Multiple roles in the therapy of neurodegenerative disorders Parkinsonism Relat. Disord. 6 (2000) 25-47. 

Various workers have detected, in addition to soluble and particle-bound trehalases, multiple forms of trehalase in some organisms. Thus, Hill and Sussman found several peaks of trehalase activity when extracts of Neurospora crassa were purified on columns of DEAE-cellulose. These various peaks were similar with respect to substrate specificity and the effect of inhibitors. Multiple forms of trehalase have also been found in blowflies, by Friedman and Alexander, and in silkmoth, by Saito. ... 

Fig. 5. Protein folding. The unfolded polypeptide chain coUapses and assembles to form simple stmctural motifs such as -sheets and a-hehces by nucleation-condensation mechanisms involving the formation of hydrogen bonds and van der Waal s interactions. Small proteins (eg, chymotrypsin inhibitor 2) attain their final (tertiary) stmcture in this way. Larger proteins and multiple protein assembhes aggregate by recognition and docking of multiple domains (eg, -barrels, a-helix bundles), often displaying positive cooperativity. Many noncovalent interactions, including hydrogen bonding, van der Waal s and electrostatic interactions, and the hydrophobic effect are exploited to create the final, compact protein assembly. Further stmctural...

Extensive work has been done on corrosion inhibitors (140), activated carbon use (141—144), multiple absorption zones and packed columns (145,146), and selective absorption and desorption of gas components (147,148). Alkan olamines can also be used for acid gas removal in ammonia plants (149). 

Corrosion Inhibition. Another important property of antifreeze solutions is the corrosion protection they provide. Most cooling systems contain varied materials of constmction including multiple metals, elastomeric materials, and rigid polymeric materials. The antifreeze chosen must contain corrosion inhibitors that are compatible with all the materials in a system. Additionally, the fluid and its corrosion inhibitor package must be suitable for the operating temperatures and conditions of the system. 

FIGURE 9.20 Design of multiple ligancl activity, (a) Dual histamine HI receptor and leukotriene receptor antagonist incorporating known antihistaminic properties of cyproheptadine and LTD4. (b) Joint ACE/NEP inhibitor formed from incorporating similarities in substrate structures for both enzymes. From [57],... 

In some patients with hypertension and in all patients with cardiac failure, the renin-angiotensin system is activated to an undesired degree, burdening the heart. The consequences of diminished ANG II generation by ACE inhibitors are multiple. In patients with hypertension, blood pressure is reduced as a result... 

Antineoplastic agents that cannot be grouped under subheadings 1-9 include miltefosine which is an alkylphosphocholine that is used to treat skin metastasis of breast cancer, and crispantase which breaks down asparagine to aspartic acid and ammonia. It is active against tumor cells that lack the enzyme asparaginase, such as acute lymphoblastic leukemia cells. Side effects include irritation of the skin in the case of miltefosine and anaphylactic reactions in the case of crispantase. Another recent development is the proteasome inhibitor bortezomib which is used to treat multiple myeloma. 

Calpain Tissue specific calpains have been implicated in diabetes, cataracts, multiple sclerosis, and limb-girdle muscular dystrophy type 2A. More than 50 inhibitors of calpain have described which have a potential for therapeutic applications. 

Multiple sclerosis (MS) 4. In rats with EAE, an animal model of multiple sclerosis, AEA and 2-AG levels are decreased in the striatum and midbrain. This might be associated with motor impairment 4. Inhibitors of degradation (both FAAH and cellular re-uptake)... 

Beyond Viagra, there are a number of other PDE inhibitors that are used clinically. In fact, the classic drugs papaverine and dipyridamole were used clinically before their effects on PDEs were known. Caffeine and theophylline (a compound found in tea) are also PDE inhibitors. However, all of these drugs most likely have multiple targets, making conclusions regarding the roles of PDEs in processes that are sensitive to these agents difficult to interpret. Certainly, some of their effects are due to their actions on adenosine receptors. 

Faivre S, Djelloul S, Raymond E (2006) New paradigms in anticancer therapy targeting multiple signaling pathways with kinase inhibitors. Semin Oncol 33 407-420... 

Another operational problem that may develop concerns multiple LP steam-heating system installations in which an imbalance in waterside chemistry results in low TDS/chemical inhibitor in one boiler and high TDS/chemical inhibitor in a second unit. 

Matthews DA, Dragovich PS, Webber SE, Fuhrman SA, Patick AK, Zalman LS, Hendrickson TF, Love RA, Prins TJ, Marakovits JT, Zhou R, Tikhe J, Ford CE, Meador JW, Ferre RA, Brown EL, Binford SL, Brothers MA, DeLisle DM, Worland ST (1999) Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes. Proc Natl Acad Sci USA 96 11000-11007... 

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