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Advancement of sialyltransferase inhibitors: therapeutic challenges and opportunities

Journal Article


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Abstract


  • Hypersialylation of tumor cell surface proteins along with a marked upregulation of sialyltransferase (ST) activity is a well-established hallmark of cancer. Due to the critical role of STs in tumor growth and progression, ST inhibition has emerged as a potential new antimetastatic strategy for a range of cancers including pancreatic and ovarian. Human STs are divided into subtypes based on their linkage and acceptor molecule, with each subtype controlling the synthesis of specific sialylated structures with unique biological roles. This has important implications for inhibitor development, as STs also play significant roles in immune responses, inflammation, viral infection, and neurological disorders. Thus, the current goal in order to advance to the clinic is the development of subtype selective, cell-permeable and synthetically accessible, small-molecule ST inhibitors. Herein is a comprehensive review of the latest developments in ST inhibitors from design, Nature, and high-throughput screening, addressing both the challenges and opportunities in targeting cell surface sialylation. The review features an overview of the biological evaluation methods, computational and imaging tools, inhibitor molecular diversity, and selectivity toward ST subtypes, along with the emerging role of ST inhibitors as diagnostic tools for disease imaging.

Publication Date


  • 2017

Citation


  • Szabo, R. & Skropeta, D. (2017). Advancement of sialyltransferase inhibitors: therapeutic challenges and opportunities. Medicinal Research Reviews, 37 (2), 219-270.

Scopus Eid


  • 2-s2.0-84990857397

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=5226&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/4202

Has Global Citation Frequency


Number Of Pages


  • 51

Start Page


  • 219

End Page


  • 270

Volume


  • 37

Issue


  • 2

Place Of Publication


  • United States

Abstract


  • Hypersialylation of tumor cell surface proteins along with a marked upregulation of sialyltransferase (ST) activity is a well-established hallmark of cancer. Due to the critical role of STs in tumor growth and progression, ST inhibition has emerged as a potential new antimetastatic strategy for a range of cancers including pancreatic and ovarian. Human STs are divided into subtypes based on their linkage and acceptor molecule, with each subtype controlling the synthesis of specific sialylated structures with unique biological roles. This has important implications for inhibitor development, as STs also play significant roles in immune responses, inflammation, viral infection, and neurological disorders. Thus, the current goal in order to advance to the clinic is the development of subtype selective, cell-permeable and synthetically accessible, small-molecule ST inhibitors. Herein is a comprehensive review of the latest developments in ST inhibitors from design, Nature, and high-throughput screening, addressing both the challenges and opportunities in targeting cell surface sialylation. The review features an overview of the biological evaluation methods, computational and imaging tools, inhibitor molecular diversity, and selectivity toward ST subtypes, along with the emerging role of ST inhibitors as diagnostic tools for disease imaging.

Publication Date


  • 2017

Citation


  • Szabo, R. & Skropeta, D. (2017). Advancement of sialyltransferase inhibitors: therapeutic challenges and opportunities. Medicinal Research Reviews, 37 (2), 219-270.

Scopus Eid


  • 2-s2.0-84990857397

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=5226&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/4202

Has Global Citation Frequency


Number Of Pages


  • 51

Start Page


  • 219

End Page


  • 270

Volume


  • 37

Issue


  • 2

Place Of Publication


  • United States