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Updated: Jul 4, 2025

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
A kinase to cytokine explorer to identify molecular regulators and potential therapeutic opportunities
Marina Chan1, Yuqi Kang1, Shannon Osborne2
1Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States.
Abstract:
Cytokines and chemokines are secreted proteins that regulate various biological processes, such as inflammation, immune response, and cell differentiation. Therefore, disruption of signaling pathways involving these proteins has been linked to a range of diseases, including cancer. However, targeting individual cytokines, chemokines, or their receptors is challenging due to their regulatory redundancy and incomplete understanding of their signaling networks. To transform these difficult-to-drug targets into a pharmacologically manageable class, we developed a web-based platform called KinCytE. This platform was designed to link the effects of kinase inhibitors, a well-established class of drugs, with cytokine and chemokine release and signaling networks. The resulting KinCytE platform enables users to investigate protein kinases that regulate specific cytokines or chemokines, generate a ranked list of FDA-approved kinase inhibitors that affect cytokine/chemokine activity, and explore and visualize cytokine signaling network thus facilitating drugging this challenging target class. KinCytE is freely accessible via https://atlas.fredhutch.org/kincyte.
Insights
This study introduces KinCytE, a web platform linking kinase inhibitors to cytokine and chemokine signaling. It helps identify drug targets for diseases like cancer by exploring kinase-cytokine networks.
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- Cytokines and chemokines are crucial secreted proteins regulating inflammation, immune responses, and cell differentiation.
- Dysregulation of these signaling pathways is implicated in various diseases, notably cancer.
- Targeting cytokines, chemokines, or their receptors is difficult due to pathway redundancy and complex signaling networks.
Purpose of the Study:
- To develop a novel web-based platform, KinCytE, to facilitate the drugging of cytokine and chemokine targets.
- To link the effects of kinase inhibitors with cytokine/chemokine release and signaling networks.
- To provide a tool for investigating protein kinases regulating specific cytokines/chemokines and identifying potential therapeutic strategies.
Main Methods:
- Development of the KinCytE web-based platform.
- Integration of data linking protein kinases to cytokine and chemokine regulation.
- Implementation of network visualization and inhibitor ranking functionalities.
Main Results:
- KinCytE enables users to identify protein kinases that modulate specific cytokine or chemokine activity.
- The platform generates a ranked list of FDA-approved kinase inhibitors impacting cytokine/chemokine activity.
- Users can explore and visualize complex cytokine signaling networks.
Conclusions:
- KinCytE transforms challenging cytokine and chemokine targets into a pharmacologically tractable class.
- The platform aids in discovering and developing kinase inhibitors for cytokine-mediated diseases.
- KinCytE offers a valuable resource for researchers investigating cytokine signaling and therapeutic interventions.
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