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Kinases, at the signaling level, dynamically mediate uncontrolled cellular growth, survival and other cancer supporting processes. This, paired with the inherent druggability of kinases, points to the importance of measuring kinase activity, and that of inhibitors against them, directly, and to analyze this accurately. High-throughput kinome profiling technologies, such as the PamStation12, allow researchers to kinetically capture kinase activity, against a multitude of peptide targets simultaneously. Yet, the complex datasets produced often require advanced computational tools and bioinformatics expertise to properly analyze that are not intuitive or readily available. To address this gap, we developed KinoViz, a web-based application to simplify analysis and visualization of kinome array data. KinoViz offers a suite of interactive tools that enables users to upload raw peptide phosphorylation datasets and conduct in-depth analyses without the need for coding knowledge. Key features include modules for visualizing kinetic phosphorylation curves, identifying statistically significant peptide changes, exploring individual peptide profiles, and generating insightful visualizations such as heatmaps, network diagrams, and dimensionality reduction plots (PCA, UMAP). By making complex kinomic data more accessible and interpretable, KinoViz allows researchers to rapidly generate interactive visualizations and comparative analyses. We aim to expand KinoViz's analytical capabilities for more advanced use, including use in direct translational drug discovery.
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http://dx.doi.org/10.21203/rs.3.rs-6431257/v1 | DOI Listing |
Int J Mol Sci
August 2025
Department of Biochemistry, Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
Disruption of the Hippo pathway leads to activation of the YAP/TAZ transcriptional program which promotes tumor initiation, progression and metastasis in diverse cancers. Aggressive triple-negative breast cancers (TNBC) lack an effective therapy; thus, inactivating YAP and TAZ has emerged as an attractive approach and a new treatment modality. Thus, we performed two complementary high-throughput RNAi-based kinome screens to uncover cancer-associated activators of YAP/TAZ in two TNBC cell lines, MDA-MB231 and MDA-MB468.
View Article and Find Full Text PDFCell Oncol (Dordr)
July 2025
Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.
Introduction: KRAS is one of the most commonly occurring mutated oncogene in human cancers. Development of KRAS G12C or G12D inhibitors exhibit promising clinical activities, but patients harboring other hotspot KRAS mutations cannot benefit from those strategies. Recent development in pan-RAS inhibitors have broad therapeutic implications and merit clinical investigation.
View Article and Find Full Text PDFKinases, at the signaling level, dynamically mediate uncontrolled cellular growth, survival and other cancer supporting processes. This, paired with the inherent druggability of kinases, points to the importance of measuring kinase activity, and that of inhibitors against them, directly, and to analyze this accurately. High-throughput kinome profiling technologies, such as the PamStation12, allow researchers to kinetically capture kinase activity, against a multitude of peptide targets simultaneously.
View Article and Find Full Text PDFCell Rep Med
July 2025
Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. Electronic address:
Precision oncology seeks to exploit tumor-specific drug sensitivities. Traditionally, this is accomplished through the identification and targeting of highly recurrent mutations. This paradigm falls short in ovarian cancer where the oncogenic alterations are more diverse, necessitating an alternate approach for the identification of tumor-specific vulnerabilities.
View Article and Find Full Text PDFJ Med Chem
May 2025
Scientific Platforms Division, Southern Research, Birmingham, Alabama 35205, United States.
Inhibition of leucine-rich repeat kinase (LRRK2) activity with small molecules has emerged as a potential novel therapeutic target for Parkinson's disease (PD). We have previously reported the identification of as a potent LRRK2 inhibitor, but the presence of a 6-thioether moiety, which is an oxidative liability, precludes its further development. Herein, we report another hit-to-lead optimization study that led to the discovery of the chiral 2,4-substituted pyrrolo[2,3-]pyrimidine series as potent LRRK2 inhibitors.
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