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KMID : 1145520210070010033
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Journal of Radiopharmaceuticals and Molecular Probes
2021 Volume.7 No. 1 p.33 ~ p.40
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Recent progress of enzyme cleavable linker in antibody?drug conjugates: sulfatase and phosphatase
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Dwivedi Sushil K.
Bhise Abhinav
Subramani Rajkumar
Yoo Jeong-Soo
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Abstract
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Recently, antibody?drug conjugates (ADCs) are used to deliver efficient cytotoxic payloads selectively in cancer cells. In the designing of an ADC, the antibody is connected to a toxic payload via a covalent linker, which helps to solubilizes the typical hydrophobic payload as well as stabilizes the linkage over circulation. The development of the linkers for the antibody drug conjugate is still in demand. Initially, the acid, disulfide, and cathepsin-sensitive ADCs attracted considerable attention for the delivery of a potent cytotoxic payload but suffer from instability in human and mouse plasma with a short half-life. In addition, It also suffer from a solubility issue that induces aggregation, which is the major problem in their development. ADCs associated with sulfatase and phosphatase cleavable linker are highly soluble due to the anionic nature of sulfate and phosphate groups. The ADCs also showed high stability in human and mouse plasma. Therefore, to overcome these limitations, sulfatase and phosphatase cleavable linkers were developed. This review focuses on the recently reported advantages of sulfatase and phosphatase cleavable linkers for ADCs.
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KEYWORD
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Cleavable linker, Antibody-drug conjugate, Sulfatase, Phosphatase
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