Chemical spaces

Application note

Analyzing In Vitro Results for the 5-HT Ligands

Chemical spaces associated with 5-ht ligands

A principal components analysis (PCA) was performed to show the chemical space covered by 5-HT ligands. Succinctly, PCA reduces the dimensionality of data, which is useful for graphical visualization. PCA latent variables were computed from 12 Burden eigenvalue (BCUT) descriptors using the MOE cheminformatic suite (4) 4. MOE, Chemical Computing Group Inc., Montreal, Canada: . These bi-dimensional descriptors incorporate both connectivity and atomic properties (atomic charge, polarizability and hydrogen bond abilities) that are relevant to intermolecular interactions.

Figure 10 displays a 3D-projection based on the first three PCAs for 803 unique 5-HT3 active structures. The resulting chemical space is relatively dispersed, reflecting the heterogeneity of chemical structures.

The same analysis was performed on active and selective 5-HT1B and 5-HT1Dligands to determine their corresponding chemical space boundaries (Figure 11). All molecules selected exhibited an affinity or activity below 200 nM and molecules that are active on both 5-HT1B and 5-HT1D were discarded. Figure 11 shows the clear overlap in space and limited regions that are more populated by either 5-HT1B or 5-HT1D ligands.

Chemical spaces associated with 5-ht ligands - Industry Insights| Elsevier R&D Solutions
Figure 10. Chemical space of a set of active 5-HT3 ligands determined by principal component analysis (PCA) using MOE chemical descriptors. Ligands were selected on the basis of biological responses available in binding or electrophysiology protocols with EC50, IC50 or Ki < 200 nM. A few specific structures are included as examples.
Active and selective 5-HT1B and 5-HT1Dligands - Industrial Insights | Elsevier R&D Solutions
Figure 11. The chemical space for a set of active and selective 5-HT1B and 5-HT1Dligands determined by principal component analysis using MOE chemical descriptors. Ligands were selected on the basis of biological responses available in binding or second messenger protocols with EC50, IC50or Ki < 200 nM on one target and > 700 nM for the other. 5-HT1Bare in red and 5-HT1D in blue.


Accessing detailed experimental data on the bioactivity of substances grants insights into the influences of protocol conditions on affinity/activity measurements. The examples examined in this paper highlight a significant spread in affinity measurements for both 5-HT1B/D and 5-HT3 ligands depending on the biological material used and other protocols conditions. By collecting and excerpting information from a vast literature base, Reaxys Medicinal Chemistry assists in defining the impact of the species and specific cell line used on in vitro binding data. Such insights can streamline assay development and lead optimization.

For effective drug discovery, an understanding of the function and therapeutic potential of a ligand should be always linked to chemical structure and druggability of the compound. Mining biological data in Reaxys Medicinal Chemistry enables a better understanding of the biological spaces associated with a target and the association to chemical structure is needed to gain a global picture.

Linking together chemistry and biology guides the efforts of medicinal chemists and pharmacologists during lead discovery and optimization phases by helping to identify innovative new structures, optimize selectivity issues and select the most appropriate and efficient test conditions to characterize compounds.

Essential drug discovery solution

Reaxys Medicinal Chemistry is an extensive database containing chemical information linked to in vitro and in vivo biological activities extracted from over 300,000 articles, 90,000 patents and 5,000 journals. More than 6 million chemical compounds are associated with their biological data (> 29 million bioactivity data points) and linked to information on 12,700 pharmacological targets, allowing the scientists to reveal connections between compounds, effects and targets. The data is indexed and normalized for maximum searchability and consistency.

Note: This application note is for illustrative purposes only: the information in this report should not be referenced or relied upon as a basis for further research and development.


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  2. Gershon, M.D. (2004) Serotonin receptors and transporters – roles in normal and abnormal gastrointestinal motility. Aliment. Pharmacol. Ther. 20: 3–14.
  3. IUPHAR receptor database:
  4. MOE, Chemical Computing Group Inc., Montreal, Canada: