Mcule.com provides a large database of purchasable compounds from multiple chemical suppliers. This large, carefully curated database is integrated with many searching and screening tools providing a powerful resource for drug discovery tasks.In this presentation we show how mcule.com can be used to identify novel histamine receptor ligands by means of ligand- and structure-based approaches available at mcule.com. Similarity searches with different descriptors by using known H1 and H4 reference ligands were able to recover several active classes. In particular, by applying linear molecular fingerprints close analogs of H1 and H4 ligands were found. Such searches and hits can be very valuable when exploring chemical space around HTS hits. On the other hand, more fuzzy descriptors were able to identify scaffolds significantly differing from those of the reference ligands. These latter searches are therefore more useful for scaffold hopping purposes. Docking into the recently discovered X-ray structure of histamine H1 receptor combined with the pharmacophore constraint optimizer feature of mcule also yielded good hit rates. It is also demonstrated how to filter out molecules with undesirable pharmacokinetic properties to keep only the most valuable hits.Since the applied tools are integrated with the high quality mcule database, the outcoming hits can be ordered directly on the website.

Exploring the chemical space of histamine receptor ligands using drug discovery tools at mcule.com

244th National Meeting (2012)

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