Biological and Medicinal Chemistry

PubChem and ChEMBL Beyond Lipinski

Jean-Louis Reymond University of Bern

Abstract

Seven million of the currently 94 million entries in the PubChem database break at least one of the four Lipinski constraints for oral bioavailability, 183,185 of which are also found in the ChEMBL database. These non-Lipinski PubChem (NLP) and ChEMBL (NLC) subsets are interesting because they contain new modalities that can display biological properties not accessible to small molecule drugs. Unfortunately, the current search tools in PubChem and ChEMBL are designed for small molecules and are not well suited to explore these subsets, which therefore remain poorly appreciated. Herein we report MXFP (macromolecule extended atom-pair fingerprint), a 217-D fingerprint tailored to analyze large molecules in terms of molecular shape and pharmacophores. We implement MXFP in two web-based applications, the first one to visualize NLP and NLC interactively using Faerun (http://faerun.gdb.tools/), the second one to perform MXFP nearest neighbor searches in NLP (http://similaritysearch.gdb.tools/). We show that these tools provide a meaningful insight into the diversity of large molecules in NLP and NLC. The interactive tools presented here are publicly available at http://gdb.unibe.ch and can be used freely to explore and better understand the diversity of non-Lipinski molecules in PubChem and ChEMBL.

Content

Thumbnail image of Lipinski-version2.pdf
download asset Lipinski-version2.pdf 2 MB [opens in a new tab]

Supplementary material

Thumbnail image of Lipinski-SI-table.docx
download asset Lipinski-SI-table.docx 0.02 MB [opens in a new tab]
Lipinski-SI-table
Thumbnail image of similaritymap-references-PubChem.txt
download asset similaritymap-references-PubChem.txt 0.14 MB [opens in a new tab]
similaritymap-references-PubChem
Thumbnail image of similaritymap-references-ChEMBL.txt
download asset similaritymap-references-ChEMBL.txt 0.08 MB [opens in a new tab]
similaritymap-references-ChEMBL

Supplementary weblinks