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Literature data on compounds both well- and poorly-absorbed in humans were used to build a statistical pattern recognition model of passive intestinal absorption. Robust outlier detection was utilized to analyze the well-absorbed compounds, some of which were intermingled with the poorly-absorbed compounds in the model space. Outliers were identified as(More)
Docking and scoring is currently one of the tools used for hit finding and hit-to-lead optimization when structural information about the target is known. Docking scores have been found useful for optimizing ligand binding to reproduce experimentally observed binding modes. The question is, can docking and scoring be used reliably for hit-to-lead(More)
This review focuses on computational methods for the prediction of passive intestinal permeability. Existing computational models are surveyed and assessed in terms of descriptors, model type/complexity, speed of computation, predictive performance, and interpretability. Challenges to the successful computational prediction of intestinal permeability, i.e.(More)
Predictive models for drug safety are crucial for helping to avoid costly late-stage failures. We review recent work on models for genotoxicity, liver toxicity, CYP450 inhibition and cardiotoxicity. These models have improved somewhat in recent years, and research has expanded into new frontiers, such as the prediction of liver toxicity. However, much more(More)
This review discusses computational methods for the prediction of drug-likeness. The coverage of published works include the assessment of historical practices of lead generation and optimization, surveys of the properties of known drugs and their constituent fragments and scaffolds, methods for delineating drug space, optimization techniques for(More)
A statistical sampling protocol is described to assess the fidelity of libraries encoded with molecular tags. The methodology, termed library QA, is based on the combined application of tag decode analysis and single bead LC/MS. The physical existence of library compounds eluted from beads is established by comparing the molecular weight predicted by tag(More)
Very large data sets of molecules screened against a broad range of targets have become available due to the advent of combinatorial chemistry. This information has led to the realization that ADME (absorption, distribution, metabolism, and excretion) and toxicity issues are important to consider prior to library synthesis. Furthermore, these large data(More)