权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

SYNTHESIS AND ANTITUMOR EVALUATION OF CC1065 ANALOGS

CC1065 类似物的合成和抗肿瘤评价

基本信息

批准号：
2716695
负责人：
YUQIANG WANG
金额：
$ 10万
依托单位：
PANORAMA RESEARCH, INC.
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-08-01 至 1999-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2716695
关键词：
analog antineoplastic antibiotics chemical synthesis cytotoxicity drug design /synthesis /production drug screening /evaluation laboratory mouse neoplasm /cancer pharmacology neoplastic cell stereoisomer

项目摘要

CC-1065 analogs are among the most potent anti-cancer drugs discovered and have unique mechanisms of antitumor action. Derivatives of CC-1065 lacking its delayed toxicity have significant antitumor activity in clinical trials. However, suppression on human bone marrow undermines their clinical effectiveness. Two new racemic CC-1065 analogs, YW-200 and YW-213 show remarkable antitumor activity in vivo without causing myelosuppression, the dose-limiting toxicity for other CC-1065 analogs. We propose to synthesize and evaluate natural enantiomeric (+)-YW-200 and (+)-YW-201, a precursor to YW-213. (+)-YW-200 and (+)-YW-201 will have improved antitumor efficacy with fewer side-effects. The overall goal of phase II is pre-clinical development with the ultimate goal of filing an IND. PROPOSED COMMERCIAL APPLICATIONS: A novel class of anti-cancer drugs has a substantial and growing market.

CC-1065 类似物是已发现的最有效的抗癌药物之一并具有独特的抗肿瘤作用机制。 CC-1065 的衍生物缺乏延迟毒性，但具有显着的抗肿瘤活性临床试验。然而，对人类骨髓的抑制会破坏他们的临床有效性。两种新的外消旋 CC-1065 类似物，YW-200 和 YW-213在体内表现出显着的抗肿瘤活性，且不会引起骨髓抑制，其他 CC-1065 类似物的剂量限制毒性。我们建议合成并评估天然对映体 (+)-YW-200 和 (+)-YW-201，YW-213 的前体。 (+)-YW-200 和 (+)-YW-201 将具有提高抗肿瘤功效，同时减少副作用。总体目标第二阶段是临床前开发，最终目标是申请 IND。拟议的商业应用：一类新型抗癌药物拥有巨大且不断增长的市场。