Biological Activity
wr-1065, a dephosphorylated metabolite of amifostine?(ethyol), can protect against the immediate and delayed effects of radiation exposure.wr-1065 can protect against zidovudine (azt) – induced genetoxicity. the lymphoblastoid cell line molt-3 cells were exposed to 0/10μm azt for 96h. in the first 24h 0/5?μm wr-1065 was added and cyt b was added in 76h in the cells, the viability of azt treated molt-3 cells did not altered.[1] moreover, in rko36 cell lines (derivative rko human colorectal carcinoma carrying a gfp-pcmv-egfp2xho), 4 mm final concentration (ec50) wr-1065 treatment for 30min immediately before irradiation showed protective effects against cell chromosomal damage and death induced by ionizing radiation and delayed genomic instability. but 40??m wr-1065 did not show immediate radio-protective effects in irradiated rko36 cells.[2] wr-1065 acts as radioprotective agents mainly through suppression of the homologous recombination pathway. in spd8 chinese hamster cell line, both 4 mm wr-1065 for 30min and 10 ?m for 24h significantly reduced the homologous recombination induced by 0.2 mm hydroxyurea for 24h or 100 nm camptothecin for 1h. while wr-1065 did not show its radioprotective effects in irradiated homologous recombination-deficient irs 1sf cells compared with homologous recombination-proficient cells aa8/cxr3(p＜0.05).[3]with spray drying technique using plga (polylactide co-glycolide) as the polymer matrix, wr-1065 were prepared into nanoparticles. 500mg/kg wr-1065/plga nanoparticles in which containing 21.7(w/w wr-1065) were administrated orally in mice to determined its radio-protective role. wr-1065plga nanoparticles treatment mice showed noteworthy higher 30-day survival, less bone marrow suppression and less intestinal injury compared non-treated control mice, indicated its significant radio-protective effects.[4]
Biochem/physiol Actions
WR-1065 is cytoprotective cell-permeable reactive oxygen species scavenger and p53 activator and re-activator. Recently shown to have antiretroviral activity and an active metabolite of Amifostine which selectively protects normal tissues from the damaging effects of anti-neoplastic radiation therapy.
References
[1]. ofelia a . olivero, michael o. ong, han nan m. braun, ariadna marrogi, kathyiani divi, james b. mitchel l, and miriam c. poirier. selective protection of zidovadine-induced dna-damage by antioxidants wr-1065 and tempol. environmental and molecular mutagenesis (2014)55: 566-572
[2]. jaroslaw dziegielewski, janet e. baulch, wilfried goetz, mitchell c. coleman, douglas r. spitz, jeffrey s. murley, david j. grdina, and william f. morgan. wr-1065, the active metabolite of amifostine, mitigates radiation-induced delayed genomic instability. free radic biol med. (2008)45(12): 1674–1681
[3]. jaroslaw dziegielewski, wilfried goetz, jeffrey s. murley, david j. grdina, william f. morgan, and janet e. baulch. amifostine metabolite wr-1065 disrupts homologous recombination in mammalian cells. radiat res. (2010) 173(2): 175–183
[4]. sarala pamujula,?vimal kishore,?barbara rider,?krishna c. agrawal, and?tarun k. mandal. radioprotection in mice following oral administration of wr-1065/plga nanoparticles. (2008) 84(11): 900-908
