ReviewJournal of medicinal chemistry2016
Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery?
Review in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
116 citing papers in PubMed.
- Defined Natural Products as Adjunctive Therapies: Evidence-Gated Polypharmacology Across Molecular Targets, Human Exposure, Clinical Signals, and Safety Boundaries.International journal of molecular sciences · 2026Review
- Plant-Derived Natural Products and Selective Apoptosis: A Cancer-Cell Vulnerability-State Framework from Redox Imbalance to Membrane-Ion Dysregulation.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Structure-Activity Relationships of Pyrrolyl-Containing Diketo Acid and Non-Diketo Acid Derivatives as Inhibitors of SARS-CoV-2 nsp13-Associated Activities.Molecules (Basel, Switzerland) · 2026Article
- Advancing Antiviral Design: Integrating Natural Products, Computation and Targeted Delivery.Chemical biology & drug design · 2026Review
- Anti-Allergic Potential of Chamaecrista nomame and Its Compound Luteolin for Novel Asthma Therapy.Phytotherapy research : PTR · 2026Article
- Antibacterial and antibiofilm activity of a triterpenoid-rich Eucalyptus globulus leaf extract against gram-positive bacteria.Scientific reports · 2026Article
- Multilevel Residual Complexity Analysis Reveals Origin of Nanomolar Antiviral Bioactives of "Isoquercitrin".Journal of natural products · 2026Article
- Lead optimization of AMS-17 identifies AMS-4 as a modulator of inflammasome-driven cocaine-associated neuroinflammation.Biochemical and biophysical research communications · 2026Article
- In Vitro Anti-Glioblastoma Activity of a Novel Pt(IV)-Ganoderic Acid A Conjugate.International journal of molecular sciences · 2026Article
- Integrating high-resolution bioassay profiling with affinity-based ligand fishing for unveiling galloylated derivatives as novel catechol-Journal of pharmaceutical analysis · 2026Article
- Rethinking network analysis in ethnopharmacology: a multi-omics and AI roadmap to overcome conceptual and methodological biases.Frontiers in pharmacology · 2026Article
- Neutrophil extracellular traps in atherosclerosis: current evidence and therapeutic potential of plant-derived metabolites.Frontiers in pharmacology · 2026Review
- A Bioinspired Approach to Mechanically Reinforce Collagen-Rich Tissues Using Modularly Defined Stilbenoids.Biopolymers · 2026Article
- Assessing biological activities of polyphenols in the context of 4R - challenges of a ubiquitous compound class with complex modes of action.Frontiers in pharmacology · 2026Review
- Antiparasitic Potential of Bioactive Compounds FromJournal of parasitology research · 2026Review
- Network Pharmacology and Machine Learning Identify Flavonoids as Potential Senotherapeutics.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Drug Repurposing to Inhibit Oncostatin M in Crohn's Disease.Molecules (Basel, Switzerland) · 2025Article
- Curcumin in Ophthalmology: Mechanisms, Challenges, and Emerging Opportunities.Molecules (Basel, Switzerland) · 2025Review
- Natural metabolites used in traditional Chinese medicine for cardiovascular diseases: pharmacological mechanisms, evidence, and future directions.Frontiers in pharmacology · 2025Review
- Building permits-control of type IV pilus assembly by PilB and its cofactors.Journal of bacteriology · 2024Review
56 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
High-throughput biology has contributed a wealth of data on chemicals, including natural products (NPs). Recently, attention was drawn to certain, predominantly synthetic, compounds that are responsible for disproportionate percentages of hits but are false actives. Spurious bioassay interference led to their designation as pan-assay interference compounds (PAINS). NPs lack comparable scrutiny, which this study aims to rectify. Systematic mining of 80+ years of the phytochemistry and biology literature, using the NAPRALERT database, revealed that only 39 compounds represent the NPs most reported by occurrence, activity, and distinct activity. Over 50% are not explained by phenomena known for synthetic libraries, and all had manifold ascribed bioactivities, designating them as invalid metabolic panaceas (IMPs). Cumulative distributions of ∼200,000 NPs uncovered that NP research follows power-law characteristics typical for behavioral phenomena. Projection into occurrence-bioactivity-effort space produces the hyperbolic black hole of NPs, where IMPs populate the high-effort base.
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What OpenQuestion holds
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.