APOPTOSIS-INDUCING ANTIMITOTIC AGENTS FOR CANCER THERAPY

描述：Cytovia发现了一类新的抗有丝分裂剂， 细胞凋亡的有效诱导剂和肿瘤细胞生长的强抑制剂。 初步实验表明，这些化合物通过以下方式阻断有丝分裂： 抑制微管蛋白的聚合，破坏微管功能，和 触发G2/M期停搏它们还可以抑制体外多药耐药细胞的生长， 耐药细胞系，这表明它们可能被证明在 治疗耐药癌症。因为这些化合物很小 合成有机分子，而不是像传统的天然产品 抗有丝分裂剂，它们可以容易地合成和修饰以产生抗有丝分裂剂。 各种各样的类似物。目前的拨款申请提出， 使用无胸腺裸鼠的这些新试剂的体内性质 癌症模型本申请还提出了设计和合成的类似物， 这些化合物，在寻找下一代抗有丝分裂剂， 优化的化学和生物学特性。建议的结果 实验将提供有关化学的关键信息， 这些抗有丝分裂剂的药理学，并将有助于确定候选人 详细的临床前测试和临床试验。 拟定商业应用： 我们建议在本申请中研究的抗有丝分裂剂似乎具有 其性质优于其他抗癌药物，包括其他抗有丝分裂剂。 如果开发成功，这些新的药物可能会捕获相当大一部分的肿瘤细胞。 抗有丝分裂抗癌药物的市场，仅紫杉烷类就可能超过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.