ArticlePLoS computational biology2014
Chemical, target, and bioactive properties of allosteric modulation.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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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
41 citing papers in PubMed, 85 citations in OpenAlex.
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
- Phosphatase Signaling as a Therapeutic Strategy in Schizophrenia.International journal of molecular sciences · 2026Review
- Negative Allosteric Modulators of AJournal of medicinal chemistry · 2025Article
- Covalent-Allosteric Inhibitors: Do We Get the Best of Both Worlds?Journal of medicinal chemistry · 2025Review
- CDK2 Allosteric Modulators: The New Route in the Design of New Drugs as Anticancer and Non-hormonal Contraceptives.Current medicinal chemistry · 2025Review
- Review
- ASD2023: towards the integrating landscapes of allosteric knowledgebase.Nucleic acids research · 2024Article
- Anthocyanins: Molecular Aspects on Their Neuroprotective Activity.Biomolecules · 2023Review
- Zafirlukast Is a Promising Scaffold for Selectively Inhibiting TNFR1 Signaling.ACS bio & med chem Au · 2023Article
- The Nonpeptide Agonist MK-5046 Functions As an Allosteric Agonist for the Bombesin Receptor Subtype-3.The Journal of pharmacology and experimental therapeutics · 2022Article
- 1-deoxysphingolipids bind to COUP-TF to modulate lymphatic and cardiac cell development.Developmental cell · 2021Article
- Cooperativity between the orthosteric and allosteric ligand binding sites of RORγt.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Annotation of Allosteric Compounds to Enhance Bioactivity Modeling for Class A GPCRs.Journal of chemical information and modeling · 2020Article
- A High-Throughput Assay to Identify Allosteric Inhibitors of the PLC-γ Isozymes Operating at Membranes.Biochemistry · 2020Article
- Impact of Allosteric Modulation in Drug Discovery: Innovation in Emerging Chemical Modalities.ACS medicinal chemistry letters · 2020Article
- Successive Statistical and Structure-Based Modeling to Identify Chemically Novel Kinase Inhibitors.Journal of chemical information and modeling · 2020Article
- Quantitative prediction of selectivity between the AJournal of cheminformatics · 2020Article
- Integrated Computational Approaches and Tools forAllosteric Drug Discovery.International journal of molecular sciences · 2020Review
- AlloDriver: a method for the identification and analysis of cancer driver targets.Nucleic acids research · 2019Article
- Computational Drug Design Applied to the Study of Metabotropic Glutamate Receptors.Molecules (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Allosteric modulators are ligands for proteins that exert their effects via a different binding site than the natural (orthosteric) ligand site and hence form a conceptually distinct class of ligands for a target of interest. Here, the physicochemical and structural features of a large set of allosteric and non-allosteric ligands from the ChEMBL database of bioactive molecules are analyzed. In general allosteric modulators are relatively smaller, more lipophilic and more rigid compounds, though large differences exist between different targets and target classes. Furthermore, there are differences in the distribution of targets that bind these allosteric modulators. Allosteric modulators are over-represented in membrane receptors, ligand-gated ion channels and nuclear receptor targets, but are underrepresented in enzymes (primarily proteases and kinases). Moreover, allosteric modulators tend to bind to their targets with a slightly lower potency (5.96 log units versus 6.66 log units, p<0.01). However, this lower absolute affinity is compensated by their lower molecular weight and more lipophilic nature, leading to similar binding efficiency and surface efficiency indices. Subsequently a series of classifier models are trained, initially target class independent models followed by finer-grained target (architecture/functional class) based models using the target hierarchy of the ChEMBL database. Applications of these insights include the selection of likely allosteric modulators from existing compound collections, the design of novel chemical libraries biased towards allosteric regulators and the selection of targets potentially likely to yield allosteric modulators on screening. All data sets used in the paper are available for download.
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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.