生物活性

• 描述DNA polymerases are essential enzymes responsible for replication and repair of DNA in all organisms^[3]. Foscarnet Sodium is a viral DNA polymerase activity inhibitor,Foscarnet sodium can inhibit dNTPs thus attenuats viral RNA polymerases, reverse transcriptase, and DNA polymerases. It is used in the treatment of cytomegalovirus retinitis^[4].The simultaneous infusion of foscarnet increased the renal clearance of lithium and its ratio to creatinine clearance as well as the urinary excretion of phosphate. Foscarnet also inhibited the lithium-induced phosphorylation of GSK3β^[5].Foscarnet in phosphate-buffered saline decreased in a dose-dependent manner the viability of cultured human skin fibroblasts. This toxic effect was markedly decreased when foscarnet was incorporated into the polymer matrix^[6].Foscarnet competes with ATP against the binding on fibroblast growth factor 2 at the heparin/ATP-binding domain. This indicates binding of foscarnet at the heparin-binding domain of FGF2. This interaction of foscarnet with fibroblast growth factor 2 reduces FGF2-induced proliferation of human umbilical vein endothelial cells and intracellular signaling via ERK1/2 kinases in this cell line^[7].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01866397	Cytomegalovirus Retinitis ... more >> Acute Renal Failure Collapse <<	Phase 4	Completed	-	Austria ... more >> Medical University of Vienna Vienna, Austria, 1190 Collapse <<
  NCT01077908	Cytomegalovirus Infection	Phase 3	Completed	-	United Kingdom ... more >> Birmingham Heartlands Hospital Birmingham, West Midlands, United Kingdom St James's University Hospital Leeds, West Yorkshire, United Kingdom, LS9 7TF Queen Elizabeth Hospital Birmingham, United Kingdom Bristol Royal Hospital for Children Bristol, United Kingdom, BS2 8BJ Addenbrookes Hospital Cambridge, United Kingdom, CB2 0QQ Beatson West of Scotland Cancer Centre Glasgow, United Kingdom Royal Liverpool Hospital Liverpool, United Kingdom University College Hospital London, United Kingdom, WC1E 6BT Kings College Hospital London, United Kingdom Royal Free Hospital London, United Kingdom Christie Hospital Manchester, United Kingdom Manchester Royal Infirmary Manchester, United Kingdom City Hospital Nottingham, United Kingdom Southampton General Hospital Southampton, United Kingdom Collapse <<
  NCT02227641	Patients Undergoing Allogeneic... more >> Stem Cell Transplantation Collapse <<	Phase 1 Phase 2	Unknown	March 2017	Germany ... more >> Medical Center Augsburg Recruiting Augsburg, Germany, 86156 Contact: Christoph Schmid, MD, PhD    0049 821 4002736       Principal Investigator: Christoph Schmid, MD, PhD          Charité University Hospital Berlin Recruiting Berlin, Germany, 13353 Contact: Armin H Gerbitz, MD, PhD    ++49 30 450565256    armin.gerbitz@charite.de    Contact: Lutz Uharek, MD, PhD       lutz.uharek@charite.de    Sub-Investigator: Lutz Uharek, MD, PhD          Principal Investigator: Armin Gerbitz, MD, PhD          Universitiy Hospital Erlangen Recruiting Erlangen, Germany, 91054 Contact: Anita Kremer, MD, PhD    ++49 9131 8543183    anita.kremer@uk-erlangen.de    Contact: Bernd Spriewald, MD, PhD    ++49 9131 8543116    bernd.spriewald@uk-erlangen.de    Sub-Investigator: Katja San Niccolo, MD          University of Mainz Recruiting Mainz, Germany, 55131 Contact: Eva Wagner, MD          Principal Investigator: Eva Wagner, MD          University of Munich LMU Recruiting Munich, Germany, 81377 Contact: Johanna Tischer, MD    0049 89 70954240       Principal Investigator: Johanna Tischer, MD          University of Regensburg Not yet recruiting Regensburg, Germany, 93053 Contact: Ernst Holler, MD, PhD    0049 941 9445570       Principal Investigator: Ernst Holler, MD, PhD Collapse <<

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• 参考文献

• [1] Rose K. Foscarnet reduces FGF2-induced proliferation of human umbilical vein endothelial cells and has antineoplastic activity against human anaplastic thyroid carcinoma cells. Biomed Pharmacother. 2013 Feb;67(1):53-7.

  [2] Oberg B. Antiviral effects of phosphonoformate (PFA, foscarnet sodium). Pharmacol Ther. 1989;40(2):213-85.

  [3] Joshua P Gill, Jun Wang,et al. DNA polymerase activity at the single-molecule level. Biochem Soc Trans.2011 Apr;39(2):595-9.

  [4] Manischewitz JF, et al. Synergistic effect of ganciclovir and foscarnet on cytomegalovirus replication in vitro.Antimicrob Agents Chemother. 1990 Feb;34(2):373-5.

  [5] Yuichi Uwai, Tatsuya Kawasaki,et al. Foscarnet, an inhibitor of the sodium-phosphate cotransporter NaPi-IIa, inhibits phosphorylation of glycogen synthase kinase-3β by lithium in the rat kidney cortex.

  [6] J Piret, A Désormeaux,et al. Sodium lauryl sulfate increases the efficacy of a topical formulation of foscarnet against herpes simplex virus type 1 cutaneous lesions in mice. Antimicrob Agents Chemother. 2000 Sep;44(9):2263-70.

  [7] Karsten Rose. Foscarnet reduces FGF2-induced proliferation of human umbilical vein endothelial cells and has antineoplastic activity against human anaplastic thyroid carcinoma cells. Biomed Pharmacother. 2013 Feb;67(1):53-7.

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