ArticleMolecular pharmacology2021
Pharmacological Characterization of the Imipridone Anticancer Drug ONC201 Reveals a Negative Allosteric Mechanism of Action at the D
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Article in Molecular pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
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
29 citing papers in PubMed, 35 citations in OpenAlex.
- A Phase 1 Randomized Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Escalating Oral Doses of Dordaviprone and the Effects of Food on the Bioavailability of Dordaviprone in Healthy Adult Subjects.Clinical pharmacology in drug development · 2025Trial
- ACTION: a randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma.Neuro-oncology · 2024Trial
- ONC201/dordaviprone for H3 K27M-mutant tumors: Discovery, mechanisms, therapeutic potential, and future directions.Genes & diseases · 2027Review
- Exon-skipping antisense oligonucleotides for H3.3K27M-altered diffuse midline glioma therapy.Molecular therapy. Nucleic acids · 2026Article
- Recent Advances in Targeted Therapies for Adult Gliomas.Current neurology and neuroscience reports · 2026Review
- Targeted therapies in pediatric oncology: A start.Molecular therapy. Oncology · 2026Review
- Development and evaluation of mitochondria-targeted caseinolytic protease (ClpP) agonist chemical probes in in vitro breast cancer models.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- The role of mitochondrial proteases in inflammation and immunity.Frontiers in immunology · 2026Review
- Successful use of response leads to ONC201 approval.Neuro-oncology · 2026Article
- Dordaviprone: First Approval.Drugs · 2026Review
- Review
- Dose Optimization of ClpP Agonists Using an In Vitro Microfluidic Perfusion Platform and In Silico Pharmacokinetic-Pharmacodynamic Modeling.The AAPS journal · 2025Article
- Neuroscience of cancer: unraveling the complex interplay between the nervous system, the tumor and the tumor immune microenvironment.Molecular cancer · 2025Review
- Pharmacological Phase I Clinical Trials in Pediatric Brain Tumors (1990-2024): A Historical Perspective.Oncology research · 2025Review
- Combining the constitutive TRAIL-secreting induced neural stem cell therapy with the novel anti-cancer drug TR-107 in glioblastoma.Molecular therapy. Oncology · 2024Article
- Demonstrated efficacy and mechanisms of sensitivity of ONC201: H3K27M-mutant diffuse midline glioma in the spotlight.Neuro-oncology · 2024Article
- Safety and pharmacokinetics of ONC201 (dordaviprone) administered two consecutive days per week in pediatric patients with H3 K27M-mutant glioma.Neuro-oncology · 2024Article
- Imipridones and Dopamine Receptor Antagonism in the Therapeutic Management of Gliomas.Advances in oncology · 2024Article
- ONC201 (Dordaviprone) in Recurrent H3 K27M-Mutant Diffuse Midline Glioma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Article
- Gemcitabine elaidate and ONC201 combination therapy for inhibiting pancreatic cancer in a KRAS mutated syngeneic mouse model.Cell death discovery · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 3 countries.
R Benjamin FreeMolecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., C.A.C., B.K.A.W., M.M.D., M.S-S., D.R.S.); Chimerix, Inc., Durham, North Carolina (V.V.P., J.E.A.); Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (B.X., L.S.); Department of Medicine, Research Institute of the McGill University Health Center (RI-MUHC), McGill University, Montréal, Canada (Y.N., S.A.P.); and Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Nottingham, Midlands, United Kingdom (J.R.L.).
Caroline A CuocoMolecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., C.A.C., B.K.A.W., M.M.D., M.S-S., D.R.S.); Chimerix, Inc., Durham, North Carolina (V.V.P., J.E.A.); Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (B.X., L.S.); Department of Medicine, Research Institute of the McGill University Health Center (RI-MUHC), McGill University, Montréal, Canada (Y.N., S.A.P.); and Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Nottingham, Midlands, United Kingdom (J.R.L.).
Bing XieMolecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., C.A.C., B.K.A.W., M.M.D., M.S-S., D.R.S.); Chimerix, Inc., Durham, North Carolina (V.V.P., J.E.A.); Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (B.X., L.S.); Department of Medicine, Research Institute of the McGill University Health Center (RI-MUHC), McGill University, Montréal, Canada (Y.N., S.A.P.); and Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Nottingham, Midlands, United Kingdom (J.R.L.).
Yoon NamkungMolecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., C.A.C., B.K.A.W., M.M.D., M.S-S., D.R.S.); Chimerix, Inc., Durham, North Carolina (V.V.P., J.E.A.); Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (B.X., L.S.); Department of Medicine, Research Institute of the McGill University Health Center (RI-MUHC), McGill University, Montréal, Canada (Y.N., S.A.P.); and Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Nottingham, Midlands, United Kingdom (J.R.L.).
Varun V PrabhuMolecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., C.A.C., B.K.A.W., M.M.D., M.S-S., D.R.S.); Chimerix, Inc., Durham, North Carolina (V.V.P., J.E.A.); Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (B.X., L.S.); Department of Medicine, Research Institute of the McGill University Health Center (RI-MUHC), McGill University, Montréal, Canada (Y.N., S.A.P.); and Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Nottingham, Midlands, United Kingdom (J.R.L.).
Blair K A WilletteMolecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., C.A.C., B.K.A.W., M.M.D., M.S-S., D.R.S.); Chimerix, Inc., Durham, North Carolina (V.V.P., J.E.A.); Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (B.X., L.S.); Department of Medicine, Research Institute of the McGill University Health Center (RI-MUHC), McGill University, Montréal, Canada (Y.N., S.A.P.); and Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Nottingham, Midlands, United Kingdom (J.R.L.).
Marilyn M DayMolecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., C.A.C., B.K.A.W., M.M.D., M.S-S., D.R.S.); Chimerix, Inc., Durham, North Carolina (V.V.P., J.E.A.); Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (B.X., L.S.); Department of Medicine, Research Institute of the McGill University Health Center (RI-MUHC), McGill University, Montréal, Canada (Y.N., S.A.P.); and Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Nottingham, Midlands, United Kingdom (J.R.L.).
Marta Sanchez-SotoMolecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., C.A.C., B.K.A.W., M.M.D., M.S-S., D.R.S.); Chimerix, Inc., Durham, North Carolina (V.V.P., J.E.A.); Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (B.X., L.S.); Department of Medicine, Research Institute of the McGill University Health Center (RI-MUHC), McGill University, Montréal, Canada (Y.N., S.A.P.); and Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Nottingham, Midlands, United Kingdom (J.R.L.).
J Robert LaneMolecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., C.A.C., B.K.A.W., M.M.D., M.S-S., D.R.S.); Chimerix, Inc., Durham, North Carolina (V.V.P., J.E.A.); Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (B.X., L.S.); Department of Medicine, Research Institute of the McGill University Health Center (RI-MUHC), McGill University, Montréal, Canada (Y.N., S.A.P.); and Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Nottingham, Midlands, United Kingdom (J.R.L.).
Stéphane A LaporteMolecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., C.A.C., B.K.A.W., M.M.D., M.S-S., D.R.S.); Chimerix, Inc., Durham, North Carolina (V.V.P., J.E.A.); Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (B.X., L.S.); Department of Medicine, Research Institute of the McGill University Health Center (RI-MUHC), McGill University, Montréal, Canada (Y.N., S.A.P.); and Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Nottingham, Midlands, United Kingdom (J.R.L.).
Lei ShiMolecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., C.A.C., B.K.A.W., M.M.D., M.S-S., D.R.S.); Chimerix, Inc., Durham, North Carolina (V.V.P., J.E.A.); Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (B.X., L.S.); Department of Medicine, Research Institute of the McGill University Health Center (RI-MUHC), McGill University, Montréal, Canada (Y.N., S.A.P.); and Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Nottingham, Midlands, United Kingdom (J.R.L.).
Joshua E AllenMolecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., C.A.C., B.K.A.W., M.M.D., M.S-S., D.R.S.); Chimerix, Inc., Durham, North Carolina (V.V.P., J.E.A.); Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (B.X., L.S.); Department of Medicine, Research Institute of the McGill University Health Center (RI-MUHC), McGill University, Montréal, Canada (Y.N., S.A.P.); and Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Nottingham, Midlands, United Kingdom (J.R.L.) sibleyd@ninds.nih.gov jallen@chimerix.com.
David R SibleyMolecular Neuropharmacology Section, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (R.B.F., C.A.C., B.K.A.W., M.M.D., M.S-S., D.R.S.); Chimerix, Inc., Durham, North Carolina (V.V.P., J.E.A.); Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland (B.X., L.S.); Department of Medicine, Research Institute of the McGill University Health Center (RI-MUHC), McGill University, Montréal, Canada (Y.N., S.A.P.); and Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Nottingham, Midlands, United Kingdom (J.R.L.) sibleyd@ninds.nih.gov jallen@chimerix.com.
Chimerix (United States) · USNational Institute on Drug Abuse · USUniversity of Nottingham · GBNational Institute of Mental Health · USNational Institute of Neurological Disorders and Stroke · USNational Institutes of Health · US
Funding
Molecular And Pharmacological Studies Of Dopamine ReceptorsZIANS002263 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI SIBLEY, DAVID · 2009 to 2025
$37.4MStructural basis for the functions of dopamine receptors, neurotransmitter transporters, and sigma 1 receptorZIADA000606 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI SHI, LEI · 2015 to 2025
$20.5MDopamine D2-like Functionally Selective AgonistsZIADA000609 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI NEWMAN, AMY HAUCK · 2016 to 2020
$2.8MIntramural NIH HHS ZIA DA000609Intramural NIH HHS ZIA NS002263
Abstract
ONC201 is a first-in-class imipridone compound that is in clinical trials for the treatment of high-grade gliomas and other advanced cancers. Recent studies identified that ONC201 antagonizes D2-like dopamine receptors at therapeutically relevant concentrations. In the current study, characterization of ONC201 using radioligand binding and multiple functional assays revealed that it was a full antagonist of the D2 and D3 receptors (D2R and D3R) with low micromolar potencies, similar to its potency for antiproliferative effects. Curve-shift experiments using D2R-mediated
Indexed as
Allosteric RegulationAnimalsAntineoplastic AgentsCHO CellsCricetinaeCricetulusDopamine D2 Receptor AntagonistsDose-Response Relationship, DrugHEK293 CellsHumansImidazolesProtein BindingProtein Structure, SecondaryPyridinesPyrimidinesReceptors, Dopamine D2Antineoplastic AgentsDopamine D2 Receptor AntagonistsDRD2 protein, humanImidazolesPyridinesPyrimidinesReceptors, Dopamine D2TIC10 compound
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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.