In Vivo Evaluation of Novel Geranylgeranyl Diphosphate Synthase Inhibitors
نویسندگان
چکیده
منابع مشابه
Characterization of potential drug targets farnesyl diphosphate synthase and geranylgeranyl diphosphate synthase in Schistosoma mansoni.
Schistosomiasis affects over 200 million people worldwide, with over 200,000 deaths annually. Currently, praziquantel is the only drug available against schistosomiasis. We report here that Schistosoma mansoni farnesyl diphosphate synthase (SmFPPS) and geranylgeranyl diphosphate synthase (SmGGPPS) are potential drug targets for the treatment of schistosomiasis. We expressed active, recombinant ...
متن کاملRecent Advances in the Development of Mammalian Geranylgeranyl Diphosphate Synthase Inhibitors.
The enzyme geranylgeranyl diphosphate synthase (GGDPS) catalyzes the synthesis of the 20-carbon isoprenoid geranylgeranyl diphosphate (GGPP). GGPP is the isoprenoid donor for protein geranylgeranylation reactions catalyzed by the enzymes geranylgeranyl transferase (GGTase) I and II. Inhibitors of GGDPS result in diminution of protein geranylgeranylation through depletion of cellular GGPP levels...
متن کاملMaize cDNAs expressed in endosperm encode functional farnesyl diphosphate synthase with geranylgeranyl diphosphate synthase activity.
Isoprenoids are the most diverse and abundant group of natural products. In plants, farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP) are precursors to many isoprenoids having essential functions. Terpenoids and sterols are derived from FPP, whereas gibberellins, carotenoids, casbenes, taxenes, and others originate from GGPP. The corresponding synthases (FPP synthase [FPPS] and G...
متن کاملSynthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase
A set of bisphosphonate ethers has been prepared through sequential phosphonylation and alkylation of monophosphonate ethers. After formation of the corresponding phosphonic acid salts, these compounds were tested for their ability to inhibit the enzyme geranylgeranyl diphosphate synthase (GGDPS). Five of the new compounds show IC50 values of less than 1 μM against GGDPS with little to no activ...
متن کاملMoiety-Linkage Map Reveals Selective Nonbisphosphonate Inhibitors of Human Geranylgeranyl Diphosphate Synthase
Bisphosphonates are potent inhibitors of farnesyl pyrophosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS). Current bisphosphonate drugs (e.g., Fosamax and Zometa) are highly efficacious in the treatment of bone diseases such as osteoporosis, Paget's disease, and tumor-induced osteolysis, but they are often less potent in blood and soft-tissue due to their phosphate moietie...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Blood
سال: 2018
ISSN: 0006-4971,1528-0020
DOI: 10.1182/blood-2018-99-113007