Perturbed functional networks fgfr signaling and allows for insights beyond traditional GO enrichment analysis. Competition experiments in chemical proteomics provide an additional layer of security to the drug target profile. Secondary and unspecific binders are difficult to distinguish from true drug targets. They are often similar in the range of peptide counts and other properties. The competition with a soluble drug and our affinity score helps in identifying biological target proteins. Interestingly, unspecific binders influence the perturbation algorithm only marginally since the proteins are dispersed all over the interactome and have no affinity to a specific uniform functional sub network. Furthermore, their binding affinity score is 0.
On the contrary, secondary binders of true drug targets increase the crosstalk to the functional PHA-739358 sub network which is attacked by the true target. Hence they can be used advantageously embedding the true targets in a specific context. In conclusion, we identified successfully known mechanisms in CML as well as potential new applications and possible sideeffects. We believe that the proposed computational approach can shed light in mechanisms of other drugs including highly promiscuous compounds and when soluble compound competition data are lacking. Introduction The root of Scutellaria baicalensis has been used as a folk medicine in China and Japan for the treatment of chronic hepatitis, allergy, thrombotic stroke and inflammatory diseases. Huangqin is known to contain numerous flavone derivatives, and their pharmacological properties have been extensively investigated.
Among them, baicalein has attracted considerable attention, as it has a variety of interesting properties, including antithrombotic, anti inflammation, anticancer, antioxidative, antimicrobial and antifibrosis activities. However, little is known about the modes of action of baicalein in these biological effects. A previous report has demonstrated that baicalein inhibits thrombininduced production of plasminogen activator inhibitor 1 incultured human umbilical vein endothelial cells. Baicalein also acts as an inhibitor of lipoxygenase in rat platelets and as a potent hypotensive compound. On the other hand, baicalein enhances vasoconstricting sensitivity to receptor dependent agonists such as noradrenaline, phenylephrine, serotonin and vasopressin in isolated rat arteries.
These studies suggest that baicalein may have a potential use in the treatment of cardiovascular disorders. In addition, baicalein exhibited remarkable antiproliferative effects on aortic smooth muscle cells. A previous study showed that baicalein was able to inhibit the migration induced by arachidonic acid and platelet derived growth factor in bovine carotid artery smooth muscle cells. Liu et al. reported that baicalein significantly inhibited the matrix metalloproteinase 2 activity and cell migration of human umbilical endothelial cells, indicating a potential role of this compound in modulation of the angiogenic process. Angiogenesis is a complex process that involves endothelial proliferation, migration, remodelling of extracellular matrix and neovessel organization. Angiogenesis also requires endothelial cell to cell, and cell to matrix interactions. New capillary blood ve