PubChem and ChEMBL beyond Lipinski

PubChem and ChEMBL beyond Lipinski

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 conta...

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Bibliographic Details
Published in:Molecular informatics Vol. 38; no. 5; pp. e1900016 - n/a
Main Authors: Capecchi, Alice, Awale, Mahendra, Probst, Daniel, Reymond, Jean‐Louis
Format: Journal Article
Language:English
Published: Germany Wiley Subscription Services, Inc 01-05-2019
Subjects:
Bioavailability
Biological properties
biomolecules
chemical space
Data bases
Databases, Pharmaceutical
Drug Evaluation, Preclinical
Fingerprints
Macromolecular Substances - analysis
Molecular Structure
Pharmaceutical Preparations - analysis
Pharmacology
PharmacoPhores
visualization
databases
visualization
chemical space
biomolecules
fingerprints
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Summary: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 and NLC (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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1868-1743
1868-1751
DOI:10.1002/minf.201900016