CHEMICAL RESEARCH IN THE DEVELOPMENT OF NEW ANTICANCER DRUGS

在该实验室合成的药物Ara-AC已开始临床应用， 三个机构的审判。 环戊烯基胞嘧啶（CPE-C）具有良好的临床前活性 针对NCI的体内肿瘤模型以及体外病毒。 CPE-C对小鼠中的标准L1210白血病肿瘤具有活性 并在抗阿糖胞苷的L1210模型中产生“治愈”。 它还 显示出对实体人肿瘤异种移植模型的优异活性 (A549肺、MX-1乳腺、转移性LOX黑素瘤）。 该化合物对DNA病毒具有突出的抗病毒活性 （HSV-1（TK+和TK-）、HSV-2、牛痘、巨细胞病毒、水痘- 带状疱疹）和RNA病毒（流感A2，水泡性口炎病毒， 日本脑炎、蓬塔托罗、裂谷热）尽管，在 在一些情况下，抗病毒治疗指数低。 基于 在其抗肿瘤活性方面，CPE-C已被选为潜在的 DTP决策网络委员会的临床候选人。

Ara-AC, a drug synthesized in this laboratory, has begun clinical trials in three institutions. Cyclopentenyl cytosine (CPE-C) has excellent preclinical activity against NCI in vivo tumor models as well as viruses in vitro. CPE-C is active against the standard L1210 leukemia tumor in mice and produces "cures" in the ara-C-resistant L1210 model. It also shows excellent activity against solid human tumor xenograft models (A549 lung, MX-1 mammary, metastatic LOX melanoma) in athymic mice. The compound has outstanding antiviral activity against DNA viruses (HSV-1 (TK+ and TK-), HSV-2, vaccinia, cytomegalovirus, varicella- zoster) and RNA viruses (influenza A2, vesicular stomatitis virus, Japanese encephalitis, Punta Toro, Rift Valley Fever) although, in several instances the antiviral therapeutic indices are low. Based on its antitumor activity, CPE-C has been selected as a potential clinical candidate by the DTP Decision Network Committee.