ArticleJournal of medicinal chemistry2012
Life beyond kinases: structure-based discovery of sorafenib as nanomolar antagonist of 5-HT receptors.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
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Who cites it
18 citing papers in PubMed, 71 citations in OpenAlex.
- Exploring Novel Antidepressants Targeting G Protein-Coupled Receptors and Key Membrane Receptors Based on Molecular Structures.Molecules (Basel, Switzerland) · 2024Review
- Molecular determinants of antagonist interactions with chemokine receptors CCR2 and CCR5.bioRxiv : the preprint server for biology · 2024Article
- The Multistage Antimalarial Compound Calxinin PerturbatesPharmaceutics · 2022Article
- A unique ligand-steered strategy for CC chemokine receptor 2 homology modeling to facilitate structure-based virtual screening.Chemical biology & drug design · 2021Article
- Low Basicity as a Characteristic for Atypical Ligands of Serotonin Receptor 5-HT2.International journal of molecular sciences · 2021Article
- Sorafenib Inhibits Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) in Hepatocellular Carcinoma Cells.Biomolecules · 2020Article
- Kinase inhibitors: the road ahead.Nature reviews. Drug discovery · 2018Review
- Unexplored therapeutic opportunities in the human genome.Nature reviews. Drug discovery · 2018Review
- 3D-e-Chem: Structural Cheminformatics Workflows for Computer-Aided Drug Discovery.ChemMedChem · 2018Article
- Structural Analysis of Chemokine Receptor-Ligand Interactions.Journal of medicinal chemistry · 2017Review
- Detecting similar binding pockets to enable systems polypharmacology.PLoS computational biology · 2017Article
- Benserazide, a dopadecarboxylase inhibitor, suppresses tumor growth by targeting hexokinase 2.Journal of experimental & clinical cancer research : CR · 2017Article
- 3D-e-Chem-VM: Structural Cheminformatics Research Infrastructure in a Freely Available Virtual Machine.Journal of chemical information and modeling · 2017Article
- Repositioning organohalogen drugs: a case study for identification of potent B-Raf V600E inhibitors via docking and bioassay.Scientific reports · 2016Article
- Integrated Approaches for Genome-wide Interrogation of the Druggable Non-olfactory G Protein-coupled Receptor Superfamily.The Journal of biological chemistry · 2015Review
- Hierarchical virtual screening approaches in small molecule drug discovery.Methods (San Diego, Calif.) · 2015Review
- A structural chemogenomics analysis of aminergic GPCRs: lessons for histamine receptor ligand design.British journal of pharmacology · 2013Article
- A public-private partnership to unlock the untargeted kinome.Nature chemical biology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Of great interest in recent years has been computationally predicting the novel polypharmacology of drug molecules. Here, we applied an "induced-fit" protocol to improve the homology models of 5-HT(2A) receptor, and we assessed the quality of these models in retrospective virtual screening. Subsequently, we computationally screened the FDA approved drug molecules against the best induced-fit 5-HT(2A) models and chose six top scoring hits for experimental assays. Surprisingly, one well-known kinase inhibitor, sorafenib, has shown unexpected promiscuous 5-HTRs binding affinities, K(i) = 1959, 56, and 417 nM against 5-HT(2A), 5-HT(2B), and 5-HT(2C), respectively. Our preliminary SAR exploration supports the predicted binding mode and further suggests sorafenib to be a novel lead compound for 5HTR ligand discovery. Although it has been well-known that sorafenib produces anticancer effects through targeting multiple kinases, carefully designed experimental studies are desirable to fully understand whether its "off-target" 5-HTR binding activities contribute to its therapeutic efficacy or otherwise undesirable side effects.
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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.