ArticleJournal of medicinal chemistry2015
An Aggregation Advisor for Ligand Discovery.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers, 1 of them a synthesis that pooled it.
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Who cites it
188 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Identifying Promiscuous Compounds with Activity against Different Target Classes.Molecules (Basel, Switzerland) · 2019Pooled it
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- Quantitative prediction of siRNA complexation by ionizable drugs enables their codelivery in nanoparticles.Science advances · 2026Article
- The rise and fall of SARM1 base-exchange inhibitors.Communications chemistry · 2026Article
- Advanced Drug Delivery Strategies for Overcoming Biological Barriers: Tumor Microenvironment and Blood-Brain Barrier.Drugs in R&D · 2026Review
- Post-Selection Methods for Analyzing mRNA Display Selections and Optimization of Hits.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Integrated Approaches in Drug Repositioning Highlight Ouabain and Helenalin as Potential Drug Candidates for Pulmonary Fibrosis.Computational and structural biotechnology journal · 2026Article
- Identification of a Quinolone-Based Scaffold as a Dual SARS-COV-2 PLᵖʳᵒ and Mᵖʳᵒ Inhibitor: An Integrated Molecular Modeling and In-vitro Evaluation Approach.Drug design, development and therapy · 2026Article
- The Discovery of Small ERK5 Inhibitors via Structure-Based Virtual Screening, Biological Evaluation and MD Simulations.Molecules (Basel, Switzerland) · 2025Article
- Membrane Perturbations and Assay Interferences by Ivermectin Explain Its In Vitro SARS-CoV-2 Antiviral Activities and Lack of Translatability.Journal of medicinal chemistry · 2025Review
- Contrastive explanations for machine learning predictions in chemistry.Journal of cheminformatics · 2025Article
- Physics-Based Solubility Prediction for Organic Molecules.Chemical reviews · 2025Review
- Employing machine learning for identifying antifungal compounds againstFuture microbiology · 2025Article
- Ultrahigh-Throughput Virtual Screening Strategies against PPI Targets: A Case Study of STAT Inhibitors.Journal of chemical information and modeling · 2025Article
- Discovery of Small-Molecule Orthopoxvirus Resolvase Inhibitors with Antiviral Activity.Journal of medicinal chemistry · 2025Article
- Mitigating Molecular Aggregation in Drug Discovery With Predictive Insights From Explainable AI.Angewandte Chemie (International ed. in English) · 2025Article
- Target Engagement Assays in Early Drug Discovery.Journal of medicinal chemistry · 2025Review
- The non-cytotoxic small molecule NPB does not inhibit BAD phosphorylation and forms colloidal aggregates.Communications medicine · 2025Article
- Screening the Pandemic Response Box identifies novel ligands of the Staphylococcus aureus protein arginine kinase, McsB.Molecular biology reports · 2025Article
128 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
Colloidal aggregation of organic molecules is the dominant mechanism for artifactual inhibition of proteins, and controls against it are widely deployed. Notwithstanding an increasingly detailed understanding of this phenomenon, a method to reliably predict aggregation has remained elusive. Correspondingly, active molecules that act via aggregation continue to be found in early discovery campaigns and remain common in the literature. Over the past decade, over 12 thousand aggregating organic molecules have been identified, potentially enabling a precedent-based approach to match known aggregators with new molecules that may be expected to aggregate and lead to artifacts. We investigate an approach that uses lipophilicity, affinity, and similarity to known aggregators to advise on the likelihood that a candidate compound is an aggregator. In prospective experimental testing, five of seven new molecules with Tanimoto coefficients (Tc's) between 0.95 and 0.99 to known aggregators aggregated at relevant concentrations. Ten of 19 with Tc's between 0.94 and 0.90 and three of seven with Tc's between 0.89 and 0.85 also aggregated. Another three of the predicted compounds aggregated at higher concentrations. This method finds that 61 827 or 5.1% of the ligands acting in the 0.1 to 10 μM range in the medicinal chemistry literature are at least 85% similar to a known aggregator with these physical properties and may aggregate at relevant concentrations. Intriguingly, only 0.73% of all drug-like commercially available compounds resemble the known aggregators, suggesting that colloidal aggregators are enriched in the literature. As a percentage of the literature, aggregator-like compounds have increased 9-fold since 1995, partly reflecting the advent of high-throughput and virtual screens against molecular targets. Emerging from this study is an aggregator advisor database and tool ( http://advisor.bkslab.org ), free to the community, that may help distinguish between fruitful and artifactual screening hits acting by this mechanism.
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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.