ArticleThe Journal of biological chemistry2020
Multimodal small-molecule screening for human prion protein binders.
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Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18citing papers in PubMed
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Who cites it
18 citing papers in PubMed.
- Phenotypic screening for small molecules that lower PrP in cultured cells.Molecular and cellular neurosciences · 2026Article
- PrP turnover in vivo and the time to effect of prion disease therapeutics.PLoS pathogens · 2026Article
- Divalent siRNA for prion disease.Nucleic acids research · 2026Article
- Phenotypic screening for small molecules that lower PrP in cultured cells.bioRxiv : the preprint server for biology · 2026Article
- Divalent siRNA for prion disease.bioRxiv : the preprint server for biology · 2026Article
- In vivo base editing extends lifespan of a humanized mouse model of prion disease.Nature medicine · 2025Article
- ShiftScan: A tool for rapid analysis of high-throughput differential scanning fluorimetry data and compound prioritization.Protein science : a publication of the Protein Society · 2025Article
- Evidence that minocycline treatment confounds the interpretation of neurofilament as a biomarker.Brain communications · 2025Article
- Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor.Science (New York, N.Y.) · 2024Article
- AI is a viable alternative to high throughput screening: a 318-target study.Scientific reports · 2024Article
- Artificial intelligence-powered discovery of small molecules inhibiting CTLA-4 in cancer.BJC reports · 2024Article
- Update on a brain-penetrant cardiac glycoside that can lower cellular prion protein levels in human and guinea pig paradigms.PloS one · 2024Article
- Modulation of prion protein expression through cryptic splice site manipulation.bioRxiv : the preprint server for biology · 2023Article
- Biomarker changes preceding symptom onset in genetic prion disease.medRxiv : the preprint server for health sciences · 2023Article
- Regional variability and genotypic and pharmacodynamic effects on PrP concentration in the CNS.JCI insight · 2022Article
- Ligands binding to the prion protein induce its proteolytic release with therapeutic potential in neurodegenerative proteinopathies.Science advances · 2021Article
- Machine Learning Prediction of Allosteric Drug Activity from Molecular Dynamics.The journal of physical chemistry letters · 2021Article
- The Compelling Demand for an Effective PrPACS medicinal chemistry letters · 2020Article
Corrections and comments
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Authors and funding
26 authors.
Andrew G ReidenbachChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Michael F MeslehCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Dominick CasalenaFacilitated Access to Screening Technologies (FAST) Lab, Novartis Institutes for Biomedical Research (NIBR), Cambridge, Massachusetts, USA.
Sonia M VallabhChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Prion Alliance, Cambridge, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
Jayme L DahlinHarvard Medical School, Boston, Massachusetts, USA; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Alison J LeedCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Alix I ChanChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Dmitry L UsanovChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Jenna B YehlCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Christopher T LemkeCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Arthur J CampbellCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Rishi N ShahUndergraduate Research Opportunities Program (UROP), Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Om K ShresthaFacilitated Access to Screening Technologies (FAST) Lab, Novartis Institutes for Biomedical Research (NIBR), Cambridge, Massachusetts, USA.
Joshua R SacherCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Victor L RangelSchool of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Jamie A MorocoCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Murugappan SathappaCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Maria Cristina NonatoSchool of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Kong T NguyenArtificial Intelligence Molecular Screen (AIMS) Awards Program, Atomwise, San Francisco, California, USA.
S Kirk WrightFacilitated Access to Screening Technologies (FAST) Lab, Novartis Institutes for Biomedical Research (NIBR), Cambridge, Massachusetts, USA.
David R LiuChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Howard Hughes Medical Institute, Chevy Chase, Maryland, USA; Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
Florence F WagnerCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Virendar K KaushikCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Douglas S AuldFacilitated Access to Screening Technologies (FAST) Lab, Novartis Institutes for Biomedical Research (NIBR), Cambridge, Massachusetts, USA.
Stuart L SchreiberChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
Eric Vallabh MinikelChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Prion Alliance, Cambridge, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA. Electronic address: eminikel@broadinstitute.org.
Funding
VASCULAR, PULMONARY AND RENAL INJURYT32HL007627 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GIMBRONE, MICHAEL A, MITCHELL, RICHARD N · 1985 to 2019
$12.7MIntegrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4MStudies of Materials with Physiological PropertiesR35GM127045 · NIGMS · BROAD INSTITUTE, INC. · PI SCHREIBER, STUART L · 2018 to 2022
$3.2MDeveloping in vitro assays to identify small molecules that inhibit human prionsF31AI122592 · NIAID · HARVARD MEDICAL SCHOOL · PI MINIKEL, ERIC VALLABH · 2016 to 2018
$99kNHLBI NIH HHS T32 HL007627NIAID NIH HHS F31 AI122592NIGMS NIH HHS R35 GM118062NIGMS NIH HHS R35 GM127045
Abstract
Prion disease is a rapidly progressive neurodegenerative disorder caused by misfolding and aggregation of the prion protein (PrP), and there are currently no therapeutic options. PrP ligands could theoretically antagonize prion formation by protecting the native protein from misfolding or by targeting it for degradation, but no validated small-molecule binders have been discovered to date. We deployed a variety of screening methods in an effort to discover binders of PrP, including
Indexed as
BenzimidazolesDrug DiscoveryDrug Evaluation, PreclinicalHumansMagnetic Resonance SpectroscopyPrion DiseasesPrion ProteinsSmall Molecule LibrariesbenzimidazoleBenzimidazolesPrion ProteinsSmall Molecule Libraries19F NMRbindersdifferential scanning fluorimetryDNA-encoded librarydrug discoverydrug screeningDSFfragment screeninghigh-throughput screening (HTS)in silico screeningneurodegenerative diseasenuclear magnetic resonance (NMR)prionprion diseasePrPsmall moleculeSTD NMRTROSY NMR
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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.