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Can I read ITK degradation to block T cell receptor signaling and overcome therapeutic resistance in T cell lymphomas on EtoBox?
ITK degradation to block T cell receptor signaling and overcome therapeutic resistance in T cell lymphomas by Baishan Jiang; David M. Weinstock; Katherine A. Donovan; Hong-Wei Sun; Ashley Wolfe; Sam Amaka; Nicholas L. Donaldson; Gongwei Wu; Yuan Jiang; Ryan A. Wilcox; Eric S. Fischer; Nathanael S. Gray; Wenchao Wu is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is ITK degradation to block T cell receptor signaling and overcome therapeutic resistance in T cell lymphomas about?
Interleukin (IL)-2-inducible T cell kinase (ITK) is essential for T cell receptor (TCR) signaling and plays an integral role in T cell proliferation and differentiation. Unlike the ITK homolog BTK, no inhibitors of ITK are currently US Food and Drug Administration (FDA) approved. In addition, recent studies have identified mutations within BTK that confer resistance to both covalent and non-covalent inhibitors. Here, as an alternative strategy, we report the development of BSJ-05-037, a potent and selective heterobifunctional degrader of ITK. BSJ-05-037 displayed enhanced anti-proliferative effects relative to its parent inhibitor BMS-509744, blocked the activation of NF-kB/GATA-3 signaling, and increased the sensitivity of T cell lymphoma cells to cytotoxic chemotherapy both in vitro and in vivo. In summary, targeted degradation of ITK is a novel approach to modulate TCR signal strength that could have broad application for the investigation and treatment of T cell-mediated diseases.
Who reads ITK degradation to block T cell receptor signaling and overcome therapeutic resistance in T cell lymphomas?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Baishan Jiang; David M. Weinstock; Katherine A. Donovan; Hong-Wei Sun; Ashley Wolfe; Sam Amaka; Nicholas L. Donaldson; Gongwei Wu; Yuan Jiang; Ryan A. Wilcox; Eric S. Fischer; Nathanael S. Gray; Wenchao Wu
- Publisher
- Elsevier BV
- Published
- 2023
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)