Polypharmacology

Phospholipase C, 24 pK0, 125, 144-145 Polar metabolites, 165 Polymorphisms, 4 Polypharmacology, 190-192 Pooled variance, 228 Populations, 226-228, 232 Positive agonism, 49 Potency... 

Knight ZA, Lin H, Shokat KM (2010) Targeting the cancer kinome through polypharmacology. Nat Rev Cancer 10 130-137... 

Aronov, A.M., McClain, B., Moody, C.S. and Murcko, M.A. (2008) Kinase-likeness and Kinase-Privileged Fragments Toward Virtual Polypharmacology. Journal of Medicinal Chemistry, 51, 1214-1222. 

Polypharmacologic effects Single receptor targeting agent... 

An In Silico Model for Interpreting Polypharmacology in Drug-Target Networks... 

Key words Frequent pattern mining, Graphs, Strings, Likelihood-ratio test, Polypharmacology,... 

Apsel B, Blair J, Gonzalez B, Nazif T, Feldman M, Aizenstein B, Hoffman R, Williams IT, Shokat K, Knight Z (2008) Targeted polypharmacology discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol 4 691-699... 

Figure 3. A diagrammatic illustration of the molecular heterogeneity in unfracdonated heparin and a rdated depolymerized agent Beside compoational variation, hq>arin and low molecular wdght heparins exhibit finctional heterogeneity in terms of its interaction with endogenous proteins and cdls The antithrombotic and anticoagulant effects of heparin are based on its polypharmacologic actions.

ApselB,BlairJA,GonzalezB,etal. Targeted polypharmacology Discovery of dualinhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 4(ll) 691-699. 

The biological activities of the different appetite suppressants are summarized in Table 15.9. Because these drugs can increase synaptic levels of multiple neurotransmitters, they often exhibit complex polypharmacology by interacting with entire families of biogenic amine receptors that often have multiple functions. 

In many cases, multiple biochemical pathways are activated by the intake of therapeutical drugs. The activation of side mechanisms coincides with the consequent side effects. This concept has led to research areas like polypharmacology as well as re-purposing studies. In such cases, the possibility of activating of multiple biochemical pathways is employed to explore alternative therapeutic uses of the same compound. In addition to the ligand-receptor process, it is necessary to take into consideration the other mechanistic features that might also be involved and affect the analysis, such as the metabolism, transport based on carry proteins, co-factors, influence of metals, etc. 

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