ArticleNature2012
Automated design of ligands to polypharmacological profiles.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 447 papers, 2 of them syntheses that pooled it.
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
447 citing papers in PubMed, 2 syntheses or guidelines pooled it, 835 citations in OpenAlex.
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- Serotonin Transporter Blockade Reduces the Psychedelic-Like Effects of 4-Methoxy-ACS chemical neuroscience · 2026Article
- Structure-guided discovery of non-catechol dopamine D1 receptor ligands with biased agonism and antagonism.The Journal of biological chemistry · 2026Article
- The Selectivity Implications of Docking Libraries with Greater and Lesser Similarities to Bio-like Molecules.Journal of medicinal chemistry · 2026Article
- Large Library Docking for Polypharmacology.Journal of medicinal chemistry · 2026Article
- The selectivity implications of docking libraries with greater and lesser similarities to bio-like molecules.bioRxiv : the preprint server for biology · 2026Article
- Dual sigma receptor 1 and 2 modulator improves memory behavior in mouse model of age-related cognitive decline.The Journal of pharmacology and experimental therapeutics · 2026Article
- Enhanced lysosomal activity prevents infection with PrPThe Journal of biological chemistry · 2026Article
- MolOrgGPT:Journal of chemical information and modeling · 2026Article
- Characterization of Novel Sigma Receptor Ligands Derived from Multicomponent Reactions as Efficacious Treatments for Neuropathic Pain.Pharmaceuticals (Basel, Switzerland) · 2026Article
- (N)-Methanocarba-adenosines as monoamine transporter allosteric inhibitors: Extended NEuropean journal of medicinal chemistry · 2026Article
- Rational antipsychotic polypharmacy in psychotic and bipolar disorders: A focus on D2 receptor partial agonists.The mental health clinician · 2025Article
- Veraguamide E, a Marine Cyanobacterial Depsipeptide Targeting σJournal of natural products · 2025Article
- Discovery of Highly Selective 5-HTJournal of medicinal chemistry · 2025Article
387 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 4 countries.
Funding
Abstract
The clinical efficacy and safety of a drug is determined by its activity profile across many proteins in the proteome. However, designing drugs with a specific multi-target profile is both complex and difficult. Therefore methods to design drugs rationally a priori against profiles of several proteins would have immense value in drug discovery. Here we describe a new approach for the automated design of ligands against profiles of multiple drug targets. The method is demonstrated by the evolution of an approved acetylcholinesterase inhibitor drug into brain-penetrable ligands with either specific polypharmacology or exquisite selectivity profiles for G-protein-coupled receptors. Overall, 800 ligand-target predictions of prospectively designed ligands were tested experimentally, of which 75% were confirmed to be correct. We also demonstrate target engagement in vivo. The approach can be a useful source of drug leads when multi-target profiles are required to achieve either selectivity over other drug targets or a desired polypharmacology.
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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.