ArticleNature chemical biology2015
Dark chemical matter as a promising starting point for drug lead discovery.
Article in Nature chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed.
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- Efficient decoy selection to improve virtual screening using machine learning models.Journal of cheminformatics · 2025Article
- InertDB as a generative AI-expanded resource of biologically inactive small molecules from PubChem.Journal of cheminformatics · 2025Article
- Cell Painting: a decade of discovery and innovation in cellular imaging.Nature methods · 2025Review
- Discovering geroprotectors through the explainable artificial intelligence-based platform AgeXtend.Nature aging · 2025Article
- Advances in artificial intelligence-based technologies for increasing the quality of medical products.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2024Review
- MolCompass: multi-tool for the navigation in chemical space and visual validation of QSAR/QSPR models.Journal of cheminformatics · 2024Article
- Occurrence of "Natural Selection" in Successful Small Molecule Drug Discovery.Journal of medicinal chemistry · 2024Article
- ChemFH: an integrated tool for screening frequent false positives in chemical biology and drug discovery.Nucleic acids research · 2024Article
- Illuminating Dark Chemical Matter Using the Cell Painting Assay.Journal of medicinal chemistry · 2024Article
- Shedding Light on Dark Chemical Matter: The Discovery of a SARS-CoV-2 MInternational journal of molecular sciences · 2024Article
- Tackling assay interference associated with small molecules.Nature reviews. Chemistry · 2024Review
- Machine Learning Assisted Hit Prioritization for High Throughput Screening in Drug Discovery.ACS central science · 2024Article
- Enhancing the Small-Scale Screenable Biological Space beyond Known Chemogenomics Libraries with Gray Chemical Matter─Compounds with Novel Mechanisms from High-Throughput Screening Profiles.ACS chemical biology · 2024Article
- Medicinal polypharmacology-a scientific glossary of terminology and concepts.Frontiers in pharmacology · 2024Review
- Exploring the medicinal potential of Dark Chemical Matters (DCM) to design promising inhibitors for PLpro of SARS-CoV-2 using molecular screening and simulation approaches.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Spacial Score─A Comprehensive Topological Indicator for Small-Molecule Complexity.Journal of medicinal chemistry · 2023Article
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18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-throughput screening (HTS) is an integral part of early drug discovery. Herein, we focused on those small molecules in a screening collection that have never shown biological activity despite having been exhaustively tested in HTS assays. These compounds are referred to as 'dark chemical matter' (DCM). We quantified DCM, validated it in quality control experiments, described its physicochemical properties and mapped it into chemical space. Through analysis of prospective reporter-gene assay, gene expression and yeast chemogenomics experiments, we evaluated the potential of DCM to show biological activity in future screens. We demonstrated that, despite the apparent lack of activity, occasionally these compounds can result in potent hits with unique activity and clean safety profiles, which makes them valuable starting points for lead optimization efforts. Among the identified DCM hits was a new antifungal chemotype with strong activity against the pathogen Cryptococcus neoformans but little activity at targets relevant to human safety.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.