ArticleNature communications2019
Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia.
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Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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87citing papers in PubMed
6.3field-weighted citation impact, top 3% of its field
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Who cites it
87 citing papers in PubMed, 145 citations in OpenAlex.
- The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026Review
- Targeting IGF2BP3 in Cancer: From Molecular Structure and Biology to Early Drug Discovery.International journal of molecular sciences · 2026Review
- Ro 08-2750 increases radiation-induced cytotoxicity in DLBCL by dysregulating the DNA damage response.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026Article
- Isoform-Specific Localization Diversifies Human MSI2 Function.bioRxiv : the preprint server for biology · 2026Article
- Regulation of RNA-binding proteins by small biomolecules.Nature reviews. Molecular cell biology · 2026Review
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- RNA-Binding Proteins in Adipose Biology: From Mechanistic Understanding to Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Targeting Musashi-2 to counteract senescence and resistance in chronic myeloid leukemia: enhancing the efficacy of imatinib therapy.BMC cancer · 2025Article
- Resistance to radiation enhances metastasis by altering RNA metabolism.Science advances · 2025Article
- Deciphering the RNA recognition by Musashi-1 to design protein and RNA variants for in vitro and in vivo applications.Nucleic acids research · 2025Article
- The dual role of RNA-binding proteins: promotion of tumorigenesis, drug resistance, and emerging therapeutic targets.Acta biochimica et biophysica Sinica · 2025Article
- The Super Enhancer-Driven Long Noncoding RNA PRKCQ-AS1 Promotes Neuroblastoma Tumorigenesis by Interacting With MSI2 Protein and Is Targetable by Small Molecule Compounds.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Prognostic marker Musashi-2 modulates DNA damage response and radioresistance in diffuse large B-cell lymphoma.Frontiers in cell and developmental biology · 2025Article
- A Circular RNA Promotes Tumor Metastasis through Stabilizing MSI2 Protein in Pancreatic Ductal Adenocarcinoma.Research (Washington, D.C.) · 2025Article
- Enhanced identification of small molecules binding to hnRNPA1 via cryptic pockets mapping coupled with X-Ray fragment screening.bioRxiv : the preprint server for biology · 2024Article
- RNA binding protein ZCCHC24 promotes tumorigenicity in triple-negative breast cancer.EMBO reports · 2024Article
- Review
- Identification of an RNA-binding perturbing characteristic for thiopurine drugs and their derivatives to disrupt CELF1-RNA interaction.Nucleic acids research · 2024Article
- Probing the orthogonality and robustness of the mammalian RNA-binding protein Musashi-1 in Escherichia coli.Journal of biological engineering · 2024Article
- A novel interaction between the 5' untranslated region of the Chikungunya virus genome and Musashi RNA binding protein is essential for efficient virus genome replication.Nucleic acids research · 2024Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
32 authors at 6 institutions in 2 countries.
Gerard MinuesaMolecular Pharmacology Program, Experimental Therapeutics Center and Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
Steven K AlbaneseLouis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0003-0973-5030
Wei XieStructural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-4550-6211
Yaniv KazanskyWeill Cornell Medical College, Tri-Institutional MD-PhD Program, Rockefeller University and Sloan Kettering Institute, New York, NY, 10065, USA.
Daniel WorrollDepartment of Pharmacology, Weill Cornell Graduate School of Medical Sciences, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-7351-676X
Arthur ChowMolecular Pharmacology Program, Experimental Therapeutics Center and Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
Alexandra SchurerMolecular Pharmacology Program, Experimental Therapeutics Center and Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
Sun-Mi ParkMolecular Pharmacology Program, Experimental Therapeutics Center and Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
Christina Z RotsidesChemical Biology Program, Sloan Kettering Institute and Tri-Institutional Research Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
James TaggartMolecular Pharmacology Program, Experimental Therapeutics Center and Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
Andrea RizziComputational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-7693-2013
Levi N NadenComputational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Timothy ChouMolecular Pharmacology Program, Experimental Therapeutics Center and Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
Saroj GourkantiMolecular Pharmacology Program, Experimental Therapeutics Center and Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
Daniel CappelSchrödinger GmbH, Q7, 23, 68161, Mannheim, Germany.ORCID http://orcid.org/0000-0002-8460-7867
Maria C PassarelliComputational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Lauren FairchildComputational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Carolina AduraHigh-Throughput and Spectroscopy Resource Center, The Rockefeller University, New York, NY, 10065, USA.
J Fraser GlickmanHigh-Throughput and Spectroscopy Resource Center, The Rockefeller University, New York, NY, 10065, USA.
Jessica SchulmanHematologic Oncology Tissue Bank, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Christopher FamulareCenter for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Minal PatelCenter for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Joseph K EiblNorthern Ontario School of Medicine, Sudbury, ON, P3E 2C6, Canada.
Gregory M RossNorthern Ontario School of Medicine, Sudbury, ON, P3E 2C6, Canada.
Shibani BhattacharyaNew York Structural Biology Center, NMR Group, New York, NY, 10027, USA.
Derek S TanChemical Biology Program, Sloan Kettering Institute and Tri-Institutional Research Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-7956-9659
Christina S LeslieComputational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-4571-5910
Thijs BeumingSchrödinger, Inc., 120 West 45th Street, New York, NY, 10036, USA.
Dinshaw J PatelStructural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-9779-7778
Yehuda GoldgurStructural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
John D ChoderaComputational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0003-0542-119X
Michael G KharasMolecular Pharmacology Program, Experimental Therapeutics Center and Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA. kharasm@mskcc.org.ORCID http://orcid.org/0000-0002-1165-6991
Memorial Sloan Kettering Cancer Center · USCornell University · USNOSM University · CARockefeller University · USNew York Structural Biology Center · USSchrodinger (United States) · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MWeill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1MOverall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3MCANCER PHARMACOLOGYT32CA062948 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LORRAINE J GUDAS · 1994 to 2026
$12.1MUncovering the role for MSI2 network in hematopoietic stem cellsR01DK101989 · NIDDK · SLOAN-KETTERING INST CAN RESEARCH · PI Michael Kharas, Vijay Ganesh Sankaran · 2014 to 2026
$6.2MCharacterizing the MSI2 network in leukemiaR01CA193842 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI KHARAS, MICHAEL · 2015 to 2025
$4.1MMolecular and genetic analysis of novel Slicer-dependent miRNA pathways in bloodR01HL135564 · NHLBI · SLOAN-KETTERING INST CAN RESEARCH · PI KHARAS, MICHAEL, LAI, ERIC C · 2017 to 2020
$2.9MEXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR015495 · NCRR · NEW YORK STRUCTURAL BIOLOGY CENTER · PI RIFKIND, RICHARD A · 2000 to 2000
$2.0MPixel Array Detector for X-ray CrystallographyS10RR029205 · NCRR · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2010 to 2010
$1.8MThe role of reorganization energy in achieving selective kinase inhibition"R01GM121505 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI CHODERA, JOHN DAMON · 2017 to 2021
$1.8MUpgrade of 800 MHz SpectrometerS10OD016432 · OD · NEW YORK STRUCTURAL BIOLOGY CENTER · PI PALMER, ARTHUR G · 2014 to 2014
$600kNCI NIH HHS P30 CA008748NCI NIH HHS R01 CA193842NCI NIH HHS T32 CA062948NCRR NIH HHS C06 RR015495NCRR NIH HHS S10 RR029205NHLBI NIH HHS R01 HL135564NIDDK NIH HHS R01 DK101989NIGMS NIH HHS P41 GM103403NIGMS NIH HHS R01 GM121505NIGMS NIH HHS T32 GM007739NIH HHS S10 OD016432
Abstract
The MUSASHI (MSI) family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum of cancers including acute myeloid leukemia. We find that the small molecule Ro 08-2750 (Ro) binds directly and selectively to MSI2 and competes for its RNA binding in biochemical assays. Ro treatment in mouse and human myeloid leukemia cells results in an increase in differentiation and apoptosis, inhibition of known MSI-targets, and a shared global gene expression signature similar to shRNA depletion of MSI2. Ro demonstrates in vivo inhibition of c-MYC and reduces disease burden in a murine AML leukemia model. Thus, we identify a small molecule that targets MSI's oncogenic activity. Our study provides a framework for targeting RNA binding proteins in cancer.
Indexed as
AnimalsApoptosisFlavinsGene Expression ProfilingGene Expression Regulation, LeukemicHumansLeukemia, ExperimentalLeukemia, Myeloid, AcuteMaleMicePrimary Cell CultureProto-Oncogene Proteins c-mycPteridinesRNARNA-Binding ProteinsRNA Recognition Motif2,3,4,10-tetrahydro-7,10-dimethyl-2,4-dioxobenzo(g)pteridineFlavinsMsi2h protein, mouseMYC protein, humanProto-Oncogene Proteins c-mycPteridinesRNARNA-Binding ProteinsRNA, Small Interfering
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