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Therapeutic potential of fucosyltransferases in cancer and recent development of targeted inhibitors

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DRUG DISCOVERY TODAY
卷 28, 期 1, 页码 -

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ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2022.103394

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Glycosylation; Fucosyltransferases; Crystal structures; Inhibitors; Cancer therapy

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FUTs play significant roles in cancer development, contributing to abnormal events such as uncontrolled cell proliferation, invasion, angiogenesis, metastasis, immune evasion, and therapy resistance. They have become attractive therapeutic targets for solid cancers, and many substrate analogs have been discovered as potential FUT inhibitors. The development of FUT protein structures has also advanced the design of nonsubstrate-based FUT inhibitors.
Fucosyltransferases (FUTs) have significant roles in various pathophysiological events. Their high expression is a signature of malignant cell transformation, contributing to many abnormal events during cancer development, such as uncontrolled cell proliferation, tumor cell invasion, angiogenesis, metastasis, immune evasion, and therapy resistance. Therefore, FUTs have evolved as an attractive therapeutic target for treating solid cancers, and many substrate analogs have been discovered with potential as FUT inhibitors for cancer therapy. Meanwhile, the development of FUT protein structures represents a significant advance in the design of FUT inhibitors with nonsubstrate structures. In this review, we summarize the role of FUTs in cancers, the resolved protein crystal structures and progress in the development of FUT inhibitors as cancer therapeutics.

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