ArticleMolecular cancer therapeutics2011
Identification of small-molecule inhibitors of the colorectal cancer oncogene Krüppel-like factor 5 expression by ultrahigh-throughput screening.
Article in Molecular cancer therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Activin A signaling stimulates neutrophil activation and macrophage migration in pancreatitis.Scientific reports · 2024Article
- Article
- KLF5 and p53 comprise an incoherent feed-forward loop directing cell-fate decisions following stress.Cell death & disease · 2023Article
- Review
- AUM302, a novel triple kinase PIM/PI3K/mTOR inhibitor, is a potent in vitro pancreatic cancer growth inhibitor.PloS one · 2023Article
- Simvastatin treatment promotes proliferation of human dental pulp stem cells via modulating PI3K/AKT/miR-9/KLF5 signalling pathway.Journal of cellular and molecular medicine · 2021Article
- The roles and regulation of the KLF5 transcription factor in cancers.Cancer science · 2021Review
- Mifepristone Derivative FZU-00,003 Suppresses Triple-negative Breast Cancer Cell Growth partially via miR-153-KLF5 axis.International journal of biological sciences · 2020Article
- The Novel Small-Molecule SR18662 Efficiently Inhibits the Growth of Colorectal CancerMolecular cancer therapeutics · 2019Article
- Krϋppel-like factors (KLFs) in renal physiology and disease.EBioMedicine · 2019Review
- Krüppel-like Factor 5, Increased in Pancreatic Ductal Adenocarcinoma, Promotes Proliferation, Acinar-to-Ductal Metaplasia, Pancreatic Intraepithelial Neoplasia, and Tumor Growth in Mice.Gastroenterology · 2018Article
- Expression of transcription factor genes in cell lines corresponding to different stages of pancreatic cancer progression.Doklady. Biochemistry and biophysics · 2017Article
- SP and KLF Transcription Factors in Digestive Physiology and Diseases.Gastroenterology · 2017Review
- Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression.Theranostics · 2016Article
- ML264, A Novel Small-Molecule Compound That Potently Inhibits Growth of Colorectal Cancer.Molecular cancer therapeutics · 2016Article
- Beyond proliferation: KLF5 promotes angiogenesis of bladder cancer through directly regulating VEGFA transcription.Oncotarget · 2015Article
- BAP1 promotes breast cancer cell proliferation and metastasis by deubiquitinating KLF5.Nature communications · 2015Article
- Kruppel-like factors in muscle health and disease.Trends in cardiovascular medicine · 2015Review
- The Krüppel-like factors in female reproductive system pathologies.Journal of molecular endocrinology · 2015Review
- [Advances of lentiviral vectors].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2014Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
The transcription factor Krüppel-like factor 5 (KLF5) is primarily expressed in the proliferative zone of the mammalian intestinal epithelium, where it regulates cell proliferation. Studies showed that inhibition of KLF5 expression reduces proliferation rates in human colorectal cancer cells and intestinal tumor formation in mice. To identify chemical probes that decrease levels of KLF5, we used cell-based ultrahigh-throughput screening (uHTS) to test compounds in the public domain of NIH, the Molecular Libraries Probe Production Centers Network library. The primary screen involved luciferase assays in the DLD-1/pGL4.18hKLF5p cell line, which stably expressed a luciferase reporter driven by the human KLF5 promoter. A cytotoxicity counterscreen was done in the rat intestinal epithelial cell line, IEC-6. We identified 97 KLF5-selective compounds with EC(50) < 10 μmol/L for KLF5 inhibition and EC(50) > 10 μmol/L for IEC-6 cytotoxicity. The two most potent compounds, CIDs (PubChem Compound IDs) 439501 and 5951923, were further characterized on the basis of computational, Western blot, and cell viability analyses. Both of these compounds, and two newly synthesized structural analogs of CID 5951923, significantly reduced endogenous KLF5 protein levels and decreased viability of several colorectal cancer cell lines without any apparent impact on IEC-6 cells. Finally, when tested in the NCI-60 panel of human cancer cell lines, compound CID 5951923 was selectively active against colon cancer cells. Our results show the feasibility of uHTS in identifying novel compounds that inhibit colorectal cancer cell proliferation by targeting KLF5.
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