生物活性

• 描述9-beta-D-arabinofuranosylguanine (ara-G) is a 2'-deoxyguanosine analogue which is 70-fold more inhibitory to the growth of T- than of B-lymphoblasts. It is less potent than ara-C but far more selective in its cytotoxic effect on T-cells. ara-G is not significantly degraded by purine nucleoside phosphorylase (EC 2.4.2.1) activity in T-lymphoblasts and is metabolized to 9-beta-D-arabinofuranosylguanine 5'-triphosphate. ara-G differs from 1-beta-D-arabinofuranosylcytosine in its selectivity for cultured T-lymphoblasts and may be of use as a chemotherapeutic or immunosuppressive agent^[2]. AraG can cause hypomethylation of DNA and induce the expression of the fetal hemoglobin gamma gene and the ABCB1 gene^[3]. Evidence of araG's ability to purge bone marrow of malignant tumor cells without causing significant toxicity to normal marrow derived hematopoietic progenitor cells was documented in experiments in which 75% of lethally irradiated mice transplanted with syngeneic bone marrow, contaminated with 6C3HED tumor cells and treated ex vivo with 100 microM araG for 18 hours, survived for > 250 to > 400 days^[4].
• 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
  NCT00866671	-	-	Completed	-	Denmark ... more >> GSK Investigational Site Aahur N, Denmark GSK Investigational Site Aalborg, Denmark, DK-9100 GSK Investigational Site Koebenhavn Oe, Denmark, 2100 GSK Investigational Site Odense C, Denmark France GSK Investigational Site Bordeaux cedex, France, 33076 GSK Investigational Site Lille Cedex, France, 59037 GSK Investigational Site Nantes Cedex 1, France, 44093 GSK Investigational Site Paris Cedex 10, France, 75475 GSK Investigational Site Paris cedex 12, France, 75571 GSK Investigational Site Paris Cedex 19, France, 75935 GSK Investigational Site Vandoeuvre-Les-Nancy, France, 54511 Germany GSK Investigational Site Essen, Nordrhein-Westfalen, Germany, 45122 GSK Investigational Site Hamburg, Germany, 20246 Israel GSK Investigational Site Beer-Sheva, Israel, 84101 GSK Investigational Site Haifa, Israel, 31096 GSK Investigational Site Petach-Tikva, Israel GSK Investigational Site Ramat Gan, Israel, 52621 Italy GSK Investigational Site Bologna, Emilia-Romagna, Italy, 40137 Netherlands GSK Investigational Site Rotterdam, Netherlands, 3015 GJ Poland GSK Investigational Site Bydgoszcz, Poland GSK Investigational Site Lublin, Poland, 20-093 GSK Investigational Site Warszawa, Poland, 00-576 GSK Investigational Site Warszawa, Poland, 02-781 GSK Investigational Site Wroclaw, Poland, 50-345 Russian Federation GSK Investigational Site Krasnodar, Russian Federation, 350007 GSK Investigational Site Moscow, Russian Federation, 117997 GSK Investigational Site Moscow, Russian Federation, 119049 Spain GSK Investigational Site Barcelona, Spain, 08035 GSK Investigational Site Boadilla del Monte (Madrid), Spain, 28660 GSK Investigational Site Madrid, Spain, 28009 GSK Investigational Site Madrid, Spain, 28047 Collapse <<
  NCT03311672	Non-small Cell Lung Cancer	Phase 2	Recruiting	November 1, 2018	United States, California ... more >> University of California, San Francisco Recruiting San Francisco, California, United States, 94107 Contact: Dora Tao    415-514-6759    dora.tao@ucsf.edu Collapse <<
  NCT03007719	Bladder Cancer	Phase 2	Recruiting	December 2018	United States, California ... more >> University of California, San Francisco Recruiting San Francisco, California, United States, 94158 Contact: Julie McCluggage, RN    877-827-3222    HDFCCC.CIP@ucsf.edu    Contact: Lissa Gray, NP    877-827-3222    HDFCCC.CIP@ucsf.edu Collapse <<

• 更多
• 参考文献

• [1] Sanford M, Lyseng-Williamson KA. Nelarabine. Drugs. 2008;68(4):439-47.

  [2] Shewach DS, Daddona PE, Ashcraft E, Mitchell BS. Metabolism and selective cytotoxicity of 9-beta-D-arabinofuranosylguanine in human lymphoblasts. Cancer Res. 1985 Mar;45(3):1008-14

  [3] Fyrberg A, Peterson C, Kågedal B, Lotfi K. Induction of fetal hemoglobin and ABCB1 gene expression in 9-β-D-arabinofuranosylguanine-resistant MOLT-4 cells. Cancer Chemother Pharmacol. 2011 Sep;68(3):583-91

  [4] Gravatt LC, Chaffee S, Hebert ME, Halperin EC, Friedman HS, Kurtzberg J. Efficacy and toxicity of 9-beta-D-arabinofuranosylguanine (araG) as an agent to purge malignant T cells from murine bone marrow: application to an in vivo T-leukemia model. Leukemia. 1993 Aug;7(8):1261-7