Preclinical Evaluation of WR-151327: An Orally Active Chemotherapy Protector

摘要: Abstract Clinical trials are in progress to evaluate radio- and chemoprotection by the aminothiol 2-[(3-aminopropyl)amino]ethanethiol-dihydrogen phosphate ester (WR-2721; amifostine). Phase II III clinical studies have demonstrated that i.v. administered WR-2721 protects against toxicities of cis -diamminedichloroplatinum (II) cyclophosphamide. In preclinical murine studies, we now further characterized chemoprotective properties WR-2721, evaluated protective ability related S -3-(3-methylaminopropylamino)propylphosphorothioic acid (WR-151327) following p.o. administration. The P388 leukemia (i.p. tumor-i.p. cytotoxic drug on Day 1 after tumor) was used determine antitumor efficacy. Single dose pretreatment with i.p. normal mouse tissues chemotoxicities mitomycin C, -diammine(cyclobutanedicarboxylato)platinum (II), doxorubicin. Bone marrow suppression drug-induced lethality were reduced, without compromising activity. Pretreatment a single WR-151327 as effective protecting myelotoxicity while activity maintained. These data support development chemotherapy protector.