An Example Of In Silico Profiling

An Example Of In Silico Profiling


This whitepaper focuses on the example of a hypothetical hit structure to target the histamine H3 receptor (Figure 1).

To determine other possible targets with which this structure might interact, a chemical similarity search is necessary. Reaxys Medicinal Chemistry was used to retrieve the necessary data. Medium selectivity was chosen as this includes structures with a wider range of rings and substituents: the degree of unsaturation, form and substitution patterns of rings is extended (Figure 2A).

On completing the chemical similarity search based on the hypothetical hit structure, 1,168 compounds were found. They are involved in 2,253 reactions, have 1,672 bioactivities associated with them and show activity against 224 targets. The data were extracted from 862 citations.

Figure 1 | Industry Insights Article
Figure 1. Hypothetical hit structure to target the H3 receptor

The activity profile for all the structures that are similar to the hypothetical hit compound can be visualized using the Heatmap (Figure 2B). The pX values quantify the biological affinities and activities from 1 (low; in blue) to 15 (high; in red). The colors of the Heatmap cells represent the maximal pX retrieved for a given compound (line) against a given target (column). Grey cells indicate that qualitative data is available and the cell is white when there is no data.

The map displays all the similar structures to the hypothetical hit compound for which in vitro biological data has been mined from the literature and the associated target proteins. In this case there are 263 similar substances active against 167 targets. Figure 2A

Figure 2A

Figure 2a| Industry Insights Article

Figure 2B

Figure 2b| Industry Insights Article
Figure 2. (A) Medium chemical similarity search on the hypothetical hit structure. (B) Heatmap displaying all chemically similar compounds for the hypothetical hit structure and the related pX values for associated targets.