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Digeranyl bisphosphonate inhibits geranylgeranyl pyrophosphate synthase.
A primary cellular target of the clinical nitrogenous bisphosphonates is the isoprenoid biosynthetic pathway. Specifically these drugs inhibit the enzyme farnesyl pyrophosphate synthase and depleteExpand
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Quantitative determination of farnesyl and geranylgeranyl diphosphate levels in mammalian tissue.
Farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP) are branch point intermediates of isoprenoid biosynthesis. Inhibitors of isoprenoid biosynthesis, such as the statins andExpand
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Contact-Dependent T Cell Activation and T Cell Stopping Require Talin1
T cell–APC contact initiates T cell activation and is maintained by the integrin LFA-1. Talin1, an LFA-1 regulator, localizes to the immune synapse (IS) with unknown roles in T cell activation. InExpand
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The focal adhesion kinase inhibitor PF-562,271 impairs primary CD4+ T cell activation.
The focal adhesion kinase inhibitor, PF-562,271, is currently in clinical development for cancer, however it is not known how PF-562,271 affects T cell function. Here, we demonstrate inhibitoryExpand
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Synthesis and biological activity of isoprenoid bisphosphonates.
Bisphosphonates have been used in the clinic to treat osteoporosis and to reduce bone resorption and the accompanying pathological bone fractures that attend a number of malignancies includingExpand
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Geranylgeranyl Diphosphate Synthase: An Emerging Therapeutic Target
Proteins modified post‐translationally by geranylgeranylation have been implicated in numerous cellular processes related to human disease. In recent years, the study of protein geranylgeranylationExpand
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Isoprenoid metabolism as a therapeutic target in gram-negative pathogens.
Gram-negative Enterobacteria include a variety of human pathogens, perhaps most notably E. coli, Salmonella, Shigella, Yersinia, and Proteus. While there are treatment options for the diseases causedExpand
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The intermediate enzymes of isoprenoid metabolism as anticancer targets.
Inhibitors of isoprenoid biosynthesis are widely used to treat human disease including statins and nitrogenous bisphosphonates. Due to the importance of core human isoprenoid biosynthesis for diverseExpand
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Synthesis of a phosphoantigen prodrug that potently activates Vγ9Vδ2 T-lymphocytes.
Phosphoantigen-sensitive Vγ9Vδ2 T cells are important responders to infections and malignancy. However, the mechanisms by which phosphoantigens stimulate Vγ9Vδ2 T cells are unclear. Here, weExpand
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Inhibition of Geranylgeranyl Diphosphate Synthase Induces Apoptosis through Multiple Mechanisms and Displays Synergy with Inhibition of Other Isoprenoid Biosynthetic Enzymes
Inhibitors of isoprenoid synthesis are widely used for treatment of human diseases, including hypercholesterolemia and osteoporosis, and they have the potential to be useful for treatment of cancer.Expand
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