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Immunotherapy has revolutionized the area of cancer treatment. Although most immunotherapies now are antibodies targeting membrane checkpoint molecules, there is an increasing demand for small-molecule drugs that address intracellular pathways. The E3 ubiquitin ligase Casitas B cell lymphoma‑b (Cbl-b) has been regarded as a promising intracellular immunotherapy target. Cbl-b regulates the downstream proteins of multiple membrane receptors and co-receptors, restricting the activation of the innate and adaptive immune system. Recently, Cbl-b inhibitors have been reported with promising effects on immune surveillance activation and anti-tumor efficacy. Several molecules have entered phase Ⅰ clinical trials. In this review, the biological rationale of Cbl-b as a promising target for cancer immunotherapy and the latest research progress of Cbl-b are summarized, with special emphasis on the allosteric small-molecule inhibitors of Cbl-b. Copyright © 2024 Elsevier Ltd. All rights reserved.

Citation

Xiuqi Hu, Erdong Li, Yangguo Zhou, Qidong You, Zhengyu Jiang. Casitas b cell lymphoma‑B (Cbl-b): A new therapeutic avenue for small-molecule immunotherapy. Bioorganic & medicinal chemistry. 2024 Mar 15;102:117677

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PMID: 38457911

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