HTS analysis

Most of the QSAR software listed in Box 23.3 is readily available in PC packages (e.g. IMP), or as client-server applications such as SAS and Pipeline Pilot Some is freeware such as R or Orange. Unfortunately, much of the 

Some of the most commonly used software in QSAR studies is listed below. Many vendors sell a variety of software for OSAR. For a more comprehensive list visit the individual vendors web site or see www.ndsu.edu/qsar socyresource/software.htm. 

University of Konstanz University of Ljubljana U n iversity of Waikato 

CHAPTER 23 Quantitative Approaches to Structure-Activity Relationships 

Molecular Networks www.molecular-networks.com Adriana Code 

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Lambert CG. ChemTree HTS Analysis Software. Golden Helix, Inc. 2005 http //www.goldenhelix.com. 

Shortfalls of the common control-based HTS data analysis approach have been suggested (Gribbon et al., 2005 Malo et al., 2006). For example plate-based normalization using controls (Table 14.1) intrinsically assumes a random error distribution for all wells in a plate because of the positional bias of the controls dictated by the formats of common screening libraries. Edge effects are particularly relevant in cell-based assays and vary from plate to plate (Malo et al., 2006). Classical HTS analysis relies on non-robust statistics means and standard deviations are greatly influenced by outliers. 

From a chemist s perspective, it is necessary to interactively analyze and visualize screening results by structural scaffolds to identify chemical series that can be synthetically optimized. Depending on the business process, interactive HTS analysis from a medicinal chemistry perspective can be performed at any stage—after primary, concentration response, or secondary screening (Figure 14.1). 

High-throughput screening (HTS) Analysis of drug target interactions in a high-capacity manner. 

However, R05 criteria were misused [50] although established for drugs, they were applied in everyday practice for post-HTS analysis in lead generation and identification. This resulted in compounds that were not easily amenable to further optimization. More restrictive criteria for leadlike compounds had to be formulated [51-54]. Besides oral drug absorption, BBB permeability has recently become of... 

Researchers from BMS have detailed the results of their efforts to enhance their HTS process [34]. Their papers discuss the subjectivity of the typical chemical structure triage process as it relates to HTS analysis, a topic worth some investigation by anyone involved in this type of selection process. With the aim of reducing subjectivity in this area, the authors systematically review their filters for physicochemical properties (this topic discussed in more detail below) and unwanted chemical moieties. Much of the work is aimed at understanding and detecting promiscuous compounds - those that initially appear to be hits in many screens (this topic discussed in more detail below). Importantly, the authors have made some of the related tools available for public use. 

Kang MK, Lee WI, Hahn HT. Analysis of vacuum bag resin transfer molding process. Composites Part A Applied Science and Manufacturing, 2001 32(11) 1553-1560. DOI 10.1016/S1359-835X(01)00012-4. 

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