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Novel Triazole Bisphosphonate Geranylgeranyl Diphosphate Synthase Inhibitors

详细技术说明: Dr.Wiemer’s lab has developed a novel class of triazole bisphosphonategeranylgeranyl diphosphate synthase (GGDPS) inhibitors that can be used assingle isomers. These inhibitors are water-soluble and can be readily synthesized.These compounds target an enzyme in isoprenoid biosynthesis that allows cellsto export proteins. Protein export is important in living organisms; however, manydiseases are characterized by cells that overreact to protein synthesis andexport. These novel compounds can inhibit the export of proteins from thediseased cells, resulting in programmed cell death. Therefore, the inhibitorsrepresent a novel therapeutic strategy for the treatment of various diseases,including multiple myeloma and other types of cancers.

*Abstract: Enzymesof the isoprenoid biosynthetic pathway are the target of many drugs, due totheir importance in the export of proteins. One common therapeutic strategyused for the treatment of osteoporosis and other diseases of the bone has beeninhibition of the enzyme farnesyl diphosphate synthase (FDPS). However, inhibitors of the enzymegeranylgeranyl diphosphate synthase (GGDPS) may be a more direct means to thebiological effects desired from FDPS inhibitors. The most potent GGDPSinhibitors have typically been mixtures of isomers. Unfortunately, the precisecomposition of these isomeric mixtures is very difficult to replicate, limitingtheir clinical applicability and favoring an inhibitor that can be used as asingle isomer.

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