Activity profiles

By using this targeted approach, one can limit compound-profiling activities to areas of high likelihood of BMT and optimize the cost-effectiveness of such screening. 

Quantitation Once protein expression profiling activities characterize qualitative features, the attention turns to delineating protein interactions and mechanistic pathways responsible for disease. These studies also require rapid sequence determination/confirmation combined with accurate and sensitive quantitative analysis. The quantitation approaches would allow for direct comparison of protein amounts (absolute or relative) from a variety of cellular states. Because of the reasons stated previously, quantitative applications are likely to be less dependent on 2-DGE and rely primarily on formats that involve specific purification and/or chromatographic separation with mass spectrometry. 

Locati, M., U. Deuschle, M. L. Massardi, F. O. Martinez, M. Sironi, S. Sozzani, T. Bartfai, and A. Mantovani. 2002. Analysis of the gene expression profile activated by the CC chemokine ligand 5/RANTES and by lipopolysaccharide in human monocytes. J Immunol 168 3557. 

Figure 1 Change of the synthesis-and-testing paradigm in drug discovery research, (a) Classical situation where compound (from left to right) and data flows (right to left) are balanced, (b) Increase in synthesis and testing capacities increased data and compound flows, (c) Further increase of data flow due to increased profiling activities and introduction of data mining as a tool to extract information and knowledge.

A systematic approach to profiling active metabolites using a 96-well plate format was recently described (Shu et al., 2002). The approach is based on a rapid bioassay-guided metabolite detection and characterization. Drug metabolite mixtures (generated by various methods described below) are separated and fractions collected into microtiter plates such as 96-well plates. The fractions are then subjected to one or more relevant activity (e.g., receptor ligand binding) assays. 

All these imply inner QSAR modeling specific for the profiled activity (ligand-receptor) that is hypothesized or a known binding mechanism, involving all available data (analogues and their endpoint measured effects). 

Management should know and so should safety reps, there should be no excuse. The statements are circulated and there are the safety reps. It is a very high profile activity and it has been from the start, (manager, interviewee 121)... 

Several years ago the activation volume for aquation of the [Fe(phen)3] " cation was found to be +15.4 cm mol . Now the measurement of the overall volume change for this reaction, -4.7 cm moP, permits the construction of its complete volume profile. Activation volumes for hydroxide and cyanide attack at [Fe(bipy)3] and [Fe(phen)3] in water are also large and positive, lying between +19 and +22 cm mo These... 

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