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Recent Advances in the Discovery of Protein Kinase C Modulators Based on the Structures of Natural Protein Kinase C Activators

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The natural products teleocidins, phorbol esters, asplysiatoxin, ingenol esters, and bryostatins are all potent protein kinase C (PKC) activators. The fact that they act at the same site of PKC implied that these structurally diverse molecules might contain the common structural elements. Several pharmacophores for these compounds have been proposed based on the molecular modeling studied and experimental results. In order to prove these hypotheses various simplified analogues of these compounds are designed, synthesized, and evaluated as new PKC activators. Some of the simplified analogues demonstrated much high potency to activate PKC, which not only gives some insights how these PKC activators bind with PKC, but also provides the new leads to develop the therapeutic tools to treat the diseases related by PKC.
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Keywords: Aplysiatoxin; Bryostatin; Essential pharmacophores; Heckers model; Ingenol; Molecular modeling; Natural Protein Kinase; PKC modulators; Phorbol easter analogues; Teleocidin Analogues

Document Type: Review Article

Publication date: 2001-02-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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