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Title: Synthesis and biological activities of simplified analogs of the natural PKC ligands, bryostatin-1 and aplysiatoxin.
Authors: Irie, Kazuhiro  kyouindb  KAKEN_id  orcid (unconfirmed)
Yanagita, Ryo C
Author's alias: 入江, 一浩
Keywords: antitumor agents
protein kinase C
tumor promoters
Issue Date: Apr-2014
Publisher: wiley
Journal title: The Chemical Record
Volume: 14
Issue: 2
Start page: 251
End page: 267
Abstract: Protein kinase C (PKC) isozymes play central roles in signal transduction on the cell surface and could serve as promising therapeutic targets of intractable diseases like cancer, Alzheimer's disease, and acquired immunodeficiency syndrome (AIDS). Although natural PKC ligands like phorbol esters, ingenol esters, and teleocidins have the potential to become therapeutic leads, most of them are potent tumor promoters in mouse skin. By contrast, bryostatin-1 (bryo-1) isolated from marine bryozoan is a potent PKC activator with little tumor-promoting activity. Numerous investigations have suggested bryo-1 to be a promising therapeutic candidate for the above intractable diseases. However, there is a supply problem of bryo-1 both from natural sources and by organic synthesis. Recent approaches on the synthesis of bryo-1 have focused on its simplification, without decreasing the ability to activate PKC isozymes, to develop new medicinal leads. Another approach is to use the skeleton of natural PKC ligands to develop bryo-1 surrogates. We have recently identified 10-methyl-aplog-1 (26), a simplified analog of tumor-promoting aplysiatoxin (ATX), as a possible therapeutic lead for cancer. This review summarizes recent investigations on the simplification of natural PKC ligands, bryo-1 and ATX, to develop potential medicinal leads.
Rights: This is the peer reviewed version of the following article: Irie, K. and Yanagita, R. C. (2014), Synthesis and Biological Activities of Simplified Analogs of the Natural PKC Ligands, Bryostatin-1 and Aplysiatoxin. Chem. Rec., 14: 251–267, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1002/tcr.201300036
PubMed ID: 24677503
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