SAR Analysis

  1. Read in the file sar_structures.sdf. One way to do this is to drag and drop the file onto the DecisionSite window.
  1. DecisionSite automatically displays a SAR table. Each compound is one row in the table, and each column represents a property or test result.
  1. Explore the SAR table. Use the scrollbars to see all the columns, and all the compounds. You can click on a header to sort by that column. For example, to see the most active compounds, click on the In-vivo Actitivy header twice.

  2. Apply Filtering. Use the Query Devices to filter out compounds that don't meet the project's criteria. For example, try filtering to Mol Wt. < 500, In-vivo Activity > 70, Bioavailability > 50. Watch the number of compounds change n the lower right corner of the DecisionSite window. Scroll through the table to see all the compounds.
  1. You should be left with around 24 compounds.
  1. Plot in-vitro vs. in-vivo activity. In the Visualization menu, select New Scatter Plot. Select Edit->Reset to All to display all 960 compounds. Change the X axis to Assay #1(IC50), and the Y axis to In-vivo Activity.
  1. This initial graph needs some configuring to be useful.
  1. Configure the graph. IC50's should be displayed on a log scale. Right-click on the Assay #1(IC50) Query Device, and select Set Property->Log Scale.
  1. Now we see a trend that lower IC50's result in higher in-vivo activities.
  1. Inspect Structures. Right-click in the graph, and choose Structure Marker Labels. Now as you move the cursor over a point in the graph, its chemical structure appears. Inspect the structure of several points.

  2. Analyze SAR. The coloring shows us that many of the exceptions to the trend can be explained by their Falied status in LC/MS. But what about the clump of compounds in the lower left part of the plot? Select Tools->Structure Analytics->Structure Viewer. Mark the clump of compounds (by dragging a rectangle around them). and you will see their structures in the Structure Viewer. You may want to resize this window, or configure its Properties to display more or fewer structures at a time. Scroll to see all the marked structures.
  1. Now you can begin developing and testing hypotheses about the structural basis for the lower than expected in-vivo actitiy of these compounds.