ArticleNature chemical biology2020
Discovery of a selective inhibitor of doublecortin like kinase 1.
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Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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60citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 2% of its field
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Applications of lung cancer organoids in precision medicine: from bench to bedside.Cell communication and signaling : CCS · 2023Pooled it
- SEC14L2 contributes to tumor progression by enhancing USP5-driven RBM3 deubiquitination in pancreatic ductal adenocarcinoma.Oncogene · 2026Article
- Paradoxical non-catalytic kinase functions are driven by inhibitor-induced displacement of autoinhibitory domains.Molecular systems biology · 2026Article
- Doublecortin-like kinase 1 promotes fibroblast activation and fibrotic progression through Smad3 binding in idiopathic pulmonary fibrosis.Journal of biomedical science · 2026Article
- Patient-derived tumor organoids for new drug development: promises and challenges.Investigational new drugs · 2026Review
- Hypovirus-Induced Phosphorylation of CpIre1 Modulates Unfolded Protein Response and Virulence in Cryphonectria parasitica.Molecular plant pathology · 2026Article
- A novel D-peptide modulates DCLK1 gelsolin interactions, reducing PDAC tumor growth.Scientific reports · 2025Article
- Hypoxic stimulation of DCLK1 transcription and alternative-promoter switching fuels tumor malignancy in clear cell renal cell carcinoma.Cell death & disease · 2025Article
- Highlighting the Role of DCLK1 in Tumor Invasion and Potential for Therapeutic Intervention.Journal of cancer immunology · 2025Article
- Targeted degradation of oncogenic KRASG12V triggers antitumor immunity in lung cancer models.The Journal of clinical investigation · 2024Article
- Design and synthesis of doublecortin-like kinase 1 inhibitors and their bioactivity evaluation.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- DCLK1 mediated cooperative acceleration of EMT by avian leukosis virus subgroup J and Marek's disease virus via the Wnt/β-catenin pathway promotes tumor metastasis.Journal of virology · 2024Article
- The doublecortin-family kinase ZYG-8DCLK1 regulates microtubule dynamics and motor-driven forces to promote the stability of C. elegans acentrosomal spindles.PLoS genetics · 2024Article
- Colonic Tuft Cells: The Less-Recognized Therapeutic Targets in Inflammatory Bowel Disease and Colorectal Cancer.International journal of molecular sciences · 2024Review
- Kinome-wide siRNA screen identifies a DCLK2-TBK1 oncogenic signaling axis in clear cell renal cell carcinoma.Molecular cell · 2024Article
- Intestinal Tuft Cells: Morphology, Function, and Implications for Human Health.Annual review of physiology · 2024Review
- Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs.Experimental hematology & oncology · 2024Review
- E74-like ETS transcription factor 1 promotes the progression of pancreatic cancer by regulating doublecortin-like kinase 1/Janus kinase/signal transducer and activator of transcription pathway.American journal of cancer research · 2024Article
- Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges.Frontiers of medicine · 2023Review
- Targeting doublecortin-like kinase 1 reveals a novel strategy to circumvent chemoresistance and metastasis in ovarian cancer.Cancer letters · 2023Article
Corrections and comments
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Authors and funding
37 authors at 12 institutions in 3 countries.
Fleur M Ferguson *Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4091-7617
Behnam Nabet *Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6738-4200
Srivatsan RaghavanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Yan LiuDepartments of Biochemistry and Radiation Oncology, the University of Texas Southwestern Medical Center, Dallas, TX, USA.
Alan L LeggettDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Miljan KuljaninDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Radha L KalekarDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Annan YangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6750-0304
Shuning HeDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Jinhua WangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1214-4103
Raymond W S NgDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Rita SulahianBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Lianbo LiDepartments of Biochemistry and Radiation Oncology, the University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0003-0107-7125
Emily J PoulinCancer Research Institute and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Ling HuangCancer Research Institute and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Jost KorenDepartment of Molecular and Human Genetics, Therapeutic Innovation Center Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA.
Nora Dieguez-MartinezDepartament de Bioquímica i Biologia Molecular & Institut de Neurociencies, Facultat de Medicina. Universitat Autonoma de Barcelona, Bellaterra, Spain.
Sergio EspinosaDepartament de Bioquímica i Biologia Molecular & Institut de Neurociencies, Facultat de Medicina. Universitat Autonoma de Barcelona, Bellaterra, Spain.
Zhiyang ZengPromega Corporation, Madison, WI, USA.
Cesear R CoronaPromega Corporation, Madison, WI, USA.
James D VastaPromega Corporation, Madison, WI, USA.
Ryoma OhiDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Taebo SimChemical Kinomics Research Center, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea and KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea.
Nam Doo KimNDBio Therapeutics Inc, Incheon, Republic of Korea.
Wayne HarshbargerBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Jose M LizcanoDepartament de Bioquímica i Biologia Molecular & Institut de Neurociencies, Facultat de Medicina. Universitat Autonoma de Barcelona, Bellaterra, Spain.ORCID http://orcid.org/0000-0002-3154-5383
Matthew B RobersPromega Corporation, Madison, WI, USA.
Senthil MuthaswamyCancer Research Institute and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Charles Y LinDepartment of Molecular and Human Genetics, Therapeutic Innovation Center Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA.
A Thomas LookDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Kevin M HaigisCancer Research Institute and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Joseph D ManciasDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Brian M WolpinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Andrew J AguirreDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0701-6203
William C HahnDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2840-9791
Kenneth D WestoverDepartments of Biochemistry and Radiation Oncology, the University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0003-3653-5923
Nathanael S GrayDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA. nathanael_gray@dfci.harvard.edu.ORCID http://orcid.org/0000-0001-5354-7403
Broad Institute · USBeth Israel Deaconess Medical Center · USDana-Farber Cancer Institute · USHarvard University · USPromega (United States) · USThe University of Texas Southwestern Medical Center · USUniversitat Autònoma de Barcelona · ESBaylor College of Medicine · USBoston Children's Hospital · USBrigham and Women's Hospital · USKorea University · KRUniversity of Michigan · US
Funding
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI EL-BARDEESY, NABEEL, SELLERS, WILLIAM R · 2007 to 2023
$33.2MSTRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI LYNN BRY · 1986 to 2026
$32.4MThe Dana-Farber Cancer Institute Cancer Target Discovery and Development CenterU01CA176058 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2013 to 2021
$7.8MSystematic identification of oncogenic KRAS synthetic lethal interactionsU01CA199253 · NCI · BROAD INSTITUTE, INC. · PI HAHN, WILLIAM C. · 2015 to 2019
$3.7MSystematic interrogation of the pancreatic cancer microenvironment in patient-derived specimensU01CA224146 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2017 to 2021
$3.0MFunctional interrogation of epigenetic vulnerabilities in KRAS-mutant pancreatic cancerK08CA218420 · NCI · DANA-FARBER CANCER INST · PI AGUIRRE, ANDREW JAMES · 2017 to 2021
$886kNCI NIH HHS K08 CA218420NCI NIH HHS P50 CA127003NCI NIH HHS U01 CA176058NCI NIH HHS U01 CA199253NCI NIH HHS U01 CA224146NIDDK NIH HHS P30 DK034854
Abstract
Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool to investigate DCLK1 biology and establish its role in cancer.
Indexed as
AnimalsCarcinoma, Pancreatic DuctalCell Line, TumorCell MovementDoublecortin-Like KinasesDoublecortin ProteinDrug Screening Assays, AntitumorGene Expression RegulationHumansIntracellular Signaling Peptides and ProteinsMaleMiceMolecular Docking SimulationMolecular StructurePancreatic NeoplasmsProtein Kinase InhibitorsDCLK1 protein, humanDcx protein, ratDoublecortin-Like KinasesDoublecortin ProteinIntracellular Signaling Peptides and ProteinsProtein Kinase InhibitorsProtein Serine-Threonine Kinases
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