Integrated Analysis Identifies Interaction Patterns between Small Molecules and Pathways

Previous studies have indicated that the downstream proteins in a key pathway can be potential drug targets and that the pathway can play an important role in the action of drugs. So pathways could be considered as targets of small molecules. A link map between small molecules and pathways was constructed using gene expression profile, pathways, and gene expression of cancer cell line intervened by small molecules and then we analysed the topological characteristics of the link map. Three link patterns were identified based on different drug discovery implications for breast, liver, and lung cancer. Furthermore, molecules that significantly targeted the same pathways tended to treat the same diseases. These results can provide a valuable reference for identifying drug candidates and targets in molecularly targeted therapy.

adhesion. These 15 small molecules target only the focal adhesion pathway. Their structures are given. The differentially expressed genes in this pathway are coloured pink, while other genes in green are human disease-related genes.
clustering between 276 small molecules and 16 pathways. The corresponding cells are coloured red where small molecules link to the pathways in the M-P link map. The labels for the corresponding pathways are shown on the right of the figure. (B) Zoomed-in plot of an sM-sP link between alsterpaullone and the 24 insulin signaling pathway. The gene indicated by the arrow is the drug target of alsterpaullone.
Differentially expressed genes in this pathway are coloured pink, while other genes in green are human disease-related genes. (C) Zoomed-in plot of mM-sP links between 16 small molecules and the Cell Communication. Their structures are given. The differentially expressed genes in this pathway are coloured pink, while other genes in green are human disease-related genes.  Gap junctions contain intercellular channels that allow direct communication betwee Glycine, serine and threonine metabolism Serine is derived from 3-phospho-D-glycerate, an intermediate of glycolysis, and glyci Glycine, serine and threonine metabolism Serine is derived from 3-phospho-D-glycerate, an intermediate of glycolysis, and glyci Hematopoietic cell lineage Blood-cell development progresses from a hematopoietic stem cell (HSC), which can u Leukocyte transendothelial migration Leukocyte migaration from the blood into tissues is vital for immune surveillance and MAPK signaling pathway The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module th mTOR signaling pathway Purine metabolism Purine metabolism Purine metabolism Purine metabolism Tryptophan metabolism Tryptophan metabolism Type II diabetes mellitus "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resist Type II diabetes mellitus "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resist Tyrosine metabolism VEGF signaling pathway There is now much evidence that VEGFR-2 is the major mediator of VEGF-driven resp d into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endoth mber are positively correlated with leptin production, and negatively correlated with production of adiponectin. channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is forme channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is forme channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is forme channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is forme channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is forme channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is forme -glycerate, an intermediate of glycolysis, and glycine is derived from serine. Threonine is an essential amino acid, which animals cann -glycerate, an intermediate of glycolysis, and glycine is derived from serine. Threonine is an essential amino acid, which animals cann from a hematopoietic stem cell (HSC), which can undergo either self-renewal or differentiation into a multilineage committed proge d into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endoth se (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiati A, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Serine/threonine phosphorylation, inter A, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Serine/threonine phosphorylation, inter EGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in bo e leukocytes bind to endothelial cell adhesion molecules (CAM) and then migrate across the vascular endothelium.
ap junction channel is formed by docking of two 'hemichannels', each containing six connexins, contributed by each neighboring cell. ap junction channel is formed by docking of two 'hemichannels', each containing six connexins, contributed by each neighboring cell. ap junction channel is formed by docking of two 'hemichannels', each containing six connexins, contributed by each neighboring cell. ap junction channel is formed by docking of two 'hemichannels', each containing six connexins, contributed by each neighboring cell. ap junction channel is formed by docking of two 'hemichannels', each containing six connexins, contributed by each neighboring cell. ap junction channel is formed by docking of two 'hemichannels', each containing six connexins, contributed by each neighboring cell. ino acid, which animals cannot synthesize. In bacteria and plants, threonine is derived from aspartate. ino acid, which animals cannot synthesize. In bacteria and plants, threonine is derived from aspartate. ultilineage committed progenitor cell: a common lymphoid progenitor (CLP) or a common myeloid progenitor (CMP). e leukocytes bind to endothelial cell adhesion molecules (CAM) and then migrate across the vascular endothelium. ell proliferation, differentiation and migration.
onine phosphorylation, interaction with SOCS, regulation of the expression, modification of the cellular localization, and degradation onine phosphorylation, interaction with SOCS, regulation of the expression, modification of the cellular localization, and degradation rucial signal transducer in both physiologic and pathologic angiogenesis.