ArticleMolecular cancer2014
Small molecule kinase inhibitor LRRK2-IN-1 demonstrates potent activity against colorectal and pancreatic cancer through inhibition of doublecortin-like kinase 1.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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70 citing papers in PubMed, 116 citations in OpenAlex.
- Exosome-Enriched Hub Gene Networks Identify Diagnostic Biomarkers and Repurposable Therapeutic Targets in Endometriosis.International journal of molecular sciences · 2026Article
- A novel D-peptide modulates DCLK1 gelsolin interactions, reducing PDAC tumor growth.Scientific reports · 2025Article
- Transcriptomic-Driven Drug Repurposing Reveals SP600125 as a Promising Drug Candidate for the Treatment of Glial-Mesenchymal Transition in Glioblastoma.International journal of molecular sciences · 2025Article
- CalDAG-GEFI acts as a guanine nucleotide exchange factor for LRRK2 to regulate LRRK2 function and neurodegeneration.Science advances · 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
- Intestinal Tuft Cells: Morphology, Function, and Implications for Human Health.Annual review of physiology · 2024Review
- Correlation Between DCAMKL-1 Protein Expression and K-ras Gene Mutation in Colorectal Cancer.Cancer management and research · 2024Article
- Role of DCLK1/Hippo pathway in type II alveolar epithelial cells differentiation in acute respiratory distress syndrome.Molecular medicine (Cambridge, Mass.) · 2023Article
- Epigenetic Landscape and Therapeutic Implication of Gene Isoforms of Doublecortin-Like Kinase 1 for Cancer Stem Cells.International journal of molecular sciences · 2023Review
- Macrophage DCLK1 promotes obesity-induced cardiomyopathy via activating RIP2/TAK1 signaling pathway.Cell death & disease · 2023Article
- DCLK1 Drives EGFR-TKI-Acquired Resistance in Lung Adenocarcinoma by Remodeling the Epithelial-Mesenchymal Transition Status.Biomedicines · 2023Article
- Doublecortin-like kinase 1 activates NF-κB to induce inflammatory responses by binding directly to IKKβ.Cell death and differentiation · 2023Article
- Structure-Guided Prediction of the Functional Impact of DCLK1 Mutations on Tumorigenesis.Biomedicines · 2023Review
- Doublecortin-like kinase 1 is a therapeutic target in squamous cell carcinoma.Molecular carcinogenesis · 2023Article
- Roc, the G-domain of the Parkinson's disease-associated protein LRRK2.Trends in biochemical sciences · 2022Review
- Oncogenic functions and clinical significances of DCLK1 isoforms in colorectal cancer: a systematic review and meta-analysis.Cancer cell international · 2022Review
- Exploring the focal role of LRRK2 kinase in Parkinson's disease.Environmental science and pollution research international · 2022Review
- Article
10 more citing papers are in PubMed but not listed here.
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10 authors at 2 institutions in 1 country.
Funding
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Abstract
backgroundDoublecortin-like kinase 1 (DCLK1) is emerging as a tumor specific stem cell marker in colorectal and pancreatic cancer. Previous in vitro and in vivo studies have demonstrated the therapeutic effects of inhibiting DCLK1 with small interfering RNA (siRNA) as well as genetically targeting the DCLK1+ cell for deletion. However, the effects of inhibiting DCLK1 kinase activity have not been studied directly. Therefore, we assessed the effects of inhibiting DCLK1 kinase activity using the novel small molecule kinase inhibitor, LRRK2-IN-1, which demonstrates significant affinity for DCLK1.
resultsHere we report that LRRK2-IN-1 demonstrates potent anti-cancer activity including inhibition of cancer cell proliferation, migration, and invasion as well as induction of apoptosis and cell cycle arrest. Additionally we found that it regulates stemness, epithelial-mesenchymal transition, and oncogenic targets on the molecular level. Moreover, we show that LRRK2-IN-1 suppresses DCLK1 kinase activity and downstream DCLK1 effector c-MYC, and demonstrate that DCLK1 kinase activity is a significant factor in resistance to LRRK2-IN-1.
conclusionsGiven DCLK1's tumor stem cell marker status, a strong understanding of its biological role and interactions in gastrointestinal tumors may lead to discoveries that improve patient outcomes. The results of this study suggest that small molecule inhibitors of DCLK1 kinase should be further investigated as they may hold promise as anti-tumor stem cell drugs.
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