Affinity of setrons


Application note

Analyzing In Vitro Results for the 5-HT Ligands

Affinity of setrons for 5-ht3 receptor

The pX values for 5-HT3were displayed using Analysis View (Figure 6). A large number of molecules and their associated bioactivities are available in Reaxys Medicinal Chemistry with affinities ranging from sub-nanomolar to the millimolar concentrations (Table 1 and Figure 6).

Figure 6 | Elsevier
Figure 6. Number of 5-HT3 ligands (x-axis) per pX value (y-axis) in Reaxys Medicinal Chemistry.

The key reference drugs of the 5-HT3 agonist sub-family of the setrons are bemesetron, tropisetron and ondansetron. The full activity profile for these drugs is visualized in a Heatmap. The compound details could be assessed in detail in the “Substances” tab and data were exported for further exploration (Figure 7).

A

Figure 7A | Elsevier

B

Figure 7B | Elsevier
Figure 7. A.The Heatmap showing the full affinity/activity profile for bemesetron, tropisetron and ondansetron (in order of appearance down the left hand column). B. Full details on each drug can be explored using the Substances tab.

The pX values of the setrons were analyzed in relation to the biological material used. Experiments performed on brain or intestine tissues and on cell lines were plotted to distinguish putative differences in affinities (Figure 8). There were significant differences between pX values obtained with brain tissue versus intestine tissue and cell lines. This may be due to the very specific nature of each assay, cell line properties, and area of the brain used, making it difficult to compare results. A closer examination of the pX values from brain tissues could elucidate whether sampling from different parts of the brain could account for some discrepancies (Figure 9).

Figure 8A | ElsevierFigure 8B | Elsevier

Figure 8C | Elsevier
Figure 8. Binding affinities expressed in pX values for different setrons in mammalian cell lines and brain or intestine tissue
Figure 9 | Elsevier
Figure 9. Binding affinities expressed in pX values for different setrons in various brain tissues