| http://purl.uniprot.org/citations/21420384 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21420384 | http://www.w3.org/2000/01/rdf-schema#comment | "A class of drugs successfully used for treatment of metabolic bone diseases is the nitrogen-containing bisphosphonates (N-BPs), which act by inhibiting the vital enzyme, farnesyl pyrophosphate synthase (FPPS), of the mevalonate pathway. Inhibition of FPPS by N-BPs results in the intracellular accumulation of isopentenyl pyrophosphate (IPP) and consequently induces the biosynthesis of a cytotoxic ATP analog (ApppI). Previous cell-free data has reported that N-BPs inhibit FPPS by time-dependent manner as a result of the conformational change. This associated conformational change can be measured as an isomerization constant (K(isom)) and reflects the binding differences of the N-BPs to FPPS. In the present study, we tested the biological relevance of the calculated K(isom) values of zoledronic acid, risedronate and five experimental N-BP analogs in the cell culture model. We used IPP/ApppI formation as a surrogate marker for blocking of FPPS in the mevalonate pathway. As a result, a correlation between the time-dependent inhibition of FPPS and IPP/ApppI formation by N-BPs was observed. This outcome indicates that the time-dependent inhibition of FPPS enzyme is a biologically significant mechanism and further supports the use of the K(isom) calculations for evaluation of the overall potency of the novel FPPS inhibitors. Additionally, data illustrates that IPP/ApppI analysis is a useful method to monitor the intracellular action of drugs and drug candidates based on FPPS inhibition."xsd:string |
| http://purl.uniprot.org/citations/21420384 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.bbrc.2011.03.070"xsd:string |
| http://purl.uniprot.org/citations/21420384 | http://purl.uniprot.org/core/author | "Auriola S."xsd:string |
| http://purl.uniprot.org/citations/21420384 | http://purl.uniprot.org/core/author | "Monkkonen H."xsd:string |
| http://purl.uniprot.org/citations/21420384 | http://purl.uniprot.org/core/author | "Monkkonen J."xsd:string |
| http://purl.uniprot.org/citations/21420384 | http://purl.uniprot.org/core/author | "Dunford J.E."xsd:string |
| http://purl.uniprot.org/citations/21420384 | http://purl.uniprot.org/core/author | "Taskinen M."xsd:string |
| http://purl.uniprot.org/citations/21420384 | http://purl.uniprot.org/core/author | "Raikkonen J."xsd:string |
| http://purl.uniprot.org/citations/21420384 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21420384 | http://purl.uniprot.org/core/name | "Biochem Biophys Res Commun"xsd:string |
| http://purl.uniprot.org/citations/21420384 | http://purl.uniprot.org/core/pages | "663-667"xsd:string |
| http://purl.uniprot.org/citations/21420384 | http://purl.uniprot.org/core/title | "Correlation between time-dependent inhibition of human farnesyl pyrophosphate synthase and blockade of mevalonate pathway by nitrogen-containing bisphosphonates in cultured cells."xsd:string |
| http://purl.uniprot.org/citations/21420384 | http://purl.uniprot.org/core/volume | "407"xsd:string |
| http://purl.uniprot.org/citations/21420384 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21420384 |
| http://purl.uniprot.org/citations/21420384 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21420384 |
| http://purl.uniprot.org/uniprot/#_P14324-mappedCitation-21420384 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21420384 |
| http://purl.uniprot.org/uniprot/P14324 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/21420384 |