APOPTOSIS-INDUCING ANTIMITOTIC AGENTS FOR CANCER THERAPY

描述：Cytovia发现了一类新的抗有丝分裂药物 强大的细胞凋亡诱导剂和强大的肿瘤细胞生长抑制因子。 初步实验表明，这些化合物通过以下方式阻止有丝分裂 抑制微管蛋白聚合，破坏微管功能 触发G2/M停滞。它们还能抑制多种药物的体外生长。 耐药细胞系，这表明它们可能被证明在 耐药癌症的治疗。因为这些化合物很小 合成有机分子，而不是像常规的天然产品 抗有丝分裂药物，它们可以很容易地合成和修饰，以产生一种 种类繁多的类比。目前的赠款申请建议将 这些新型药物在裸鼠体内的特性 癌症模型。该应用程序还建议设计和合成类似的 这些化合物，在寻找下一代抗有丝分裂药物时 最优化的化学和生物特性。建议的研究结果 实验将提供有关化学和化学的关键信息 这些抗有丝分裂药物的药理学，并将有助于确定候选药物 详细的临床前测试和临床试验。 建议的商业应用： 我们计划在这一应用中研究的抗有丝分裂药物似乎具有 性能优于其他抗癌药物，包括其他抗有丝分裂药物。 如果成功开发，这些新的试剂可能会捕获很大一部分 抗肿瘤药物市场，仅紫杉烷一项就可能超过20亿美元 在2000年。

DESCRIPTION: Cytovia has discovered a new class of antimitotic agents which are potent inducers of apoptosis and strong inhibitors of tumor cell growth. Preliminary experiments indicate that these compounds block mitosis by inhibiting the polymerization of tubulin, disrupting microtubule function, and triggering G2/M arrest. They can also inhibit the in vitro growth of multidrug resistant cell lines, which suggests that they may prove useful in the treatment of drug-resistant cancers. Because these compounds are small synthetic organic molecules, rather than natural products like the conventional antimitotic agents, they can be synthesized and modified readily to produce a wide variety of analogs. The current grant application proposes to characterize the in vivo properties of these novel agents using the athymic nude mouse cancer model. The application also proposes to design and synthesize analogs of these compounds, in a search for next-generation antimitotic agents with optimized chemical and biological properties. The results of the proposed experiments will provide critical information about the chemistry and pharmacology of these antimitotic agents and will help identify candidates for detailed pre-clinical testing and clinical trials. PROPOSED COMMERCIAL APPLICATION: The antimitotic agents that we propose to study in this application appear to have properties that are superior to other anticancer drugs, including other antimitotic agents. If successfully developed, these novel agents may capture a substantial portion of the market for antimitotics cancer drugs, which for the taxanes alone may exceed $2 billion in the year 2000.