The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery?
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Natural products as sources of new drugs over the 30 years from 1981 to 2010
Newman, D. J., & Cragg, G. M. (2012) · Journal of Natural Products · doi:10.1021/np200906s · Cited by 4,687
The role of natural product chemistry in drug discovery
Butler, M. S. (2004) · Journal of Natural Products · doi:10.1021/np040106y · Cited by 1,381
Choi, Y. H., van Spronsen, J., Dai, Y., Verberne, M., Hollmann, F., Arends, I. W. C. E., Witkamp, G.-J., & Verpoorte, R. (2011) · Plant Physiology · doi:10.1104/pp.111.178426 · Cited by 1,368
Cited by
Natural products as sources of new drugs from 1981 to 2014
Newman, D. J., & Cragg, G. M. (2016) · Journal of Natural Products · doi:10.1021/acs.jnatprod.5b01055 · Cited by 5,858
The Essential Medicinal Chemistry of Curcumin
Nelson, K. M., Dahlin, J. L., Bisson, J., Graham, J., Pauli, G. F., & Walters, M. A. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00975 · Cited by 1,956
Self-citationNatural deep eutectic solvents: Properties, applications, and perspectives
Liu, Y., Friesen, J. B., McAlpine, J. B., Lankin, D. C., Chen, S.-N., & Pauli, G. F. (2018) · Journal of Natural Products · doi:10.1021/acs.jnatprod.7b00945 · Cited by 1,304
Self-citationPanossian, A. G., Efferth, T., Shikov, A. N., Pozharitskaya, O. N., Kuchta, K., Mukherjee, P. K., Banerjee, S., Heinrich, M., Wu, W., Guo, D., et al. (2021) · Medicinal Research Reviews · doi:10.1002/med.21743 · Cited by 347
Natural Products as a Source for Novel Antibiotics
Moloney, M. G. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.05.001 · Cited by 308
Metadata
- Authors
- Bisson, J., McAlpine, J. B., Friesen, J. B., Chen, S.-N., Graham, J., & Pauli, G. F.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-10-27
- Volume
- 59
- Issue
- 5
- Pages
- 1671-1690
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2234844573
- Cited by
- 247
- References
- 3
- FWCI
- 19.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery? https://app.cochat.ai/papers/10.1021/acs.jmedchem.5b01009
- The paper
- Bisson, J., McAlpine, J. B., Friesen, J. B., Chen, S.-N., Graham, J., & Pauli, G. F. (2016). Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery? Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.5b01009
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
