Antimitotic agents are among the most effective drugs for the treatment of solid tumors and metastatic cancer. These drugs promote cell death by interfering with the crucial structural and regulatory function of microtubules in cells. Most of the agents of clinical relevance are natural products or semisynthetic derivatives thereof, and they fall into two major classes: microtubule stabilizers such as the taxanes, which enhance tubulin polymerization, and microtubule destabilizers such as the Vinca alkaloids, which lead to the depolymerization of existing microtubules. While these drugs are effective in inhibiting the progression of certain types of tumors, their utility is limited in part by incomplete tumor responses and/or significant side effects. In addition, inherent resistance is encountered in many tumor types, or acquired resistance may occur as a result of multiple cycles of therapy. Cevipabulin (TTI-237) is a novel, small synthetic molecule with an unusual biological mode of action. It appears to bind at the vinca site, but exhibits some properties similar to those of taxane-site ligands, such as enhancing tubulin polymerization. The compound works against a variety of tumors, including those resistant to paclitaxel and vincristine. Furthermore, cevipabulin is stable and water-soluble, and can be administered i.v. or p.o. in saline. It can be synthesized in bulk quantities efficiently. Based on these properties, cevipabulin was selected for clinical development.

中文翻译：

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Cevipabulin（TTI-237）：一种新型抗微管剂的临床前和临床结果。

抗有丝分裂剂是用于治疗实体瘤和转移性癌症的最有效药物之一。这些药物通过干扰细胞中微管的关键结构和调节功能来促进细胞死亡。大多数具有临床意义的药物是天然产物或其半合成衍生物，它们可分为两大类：微管稳定剂（如紫杉烷，可增强微管蛋白的聚合反应）和微管去稳定剂（如长春花生物碱），可导致三聚氰胺的解聚现有的微管。尽管这些药物可有效抑制某些类型的肿瘤的进展，但其用途部分受到肿瘤反应不完全和/或明显副作用的限制。此外，在许多类型的肿瘤中都遇到固有的耐药性，或多个治疗周期可能导致获得性耐药。Cevipabulin（TTI-237）是一种新颖的小型合成分子，具有不同寻常的生物学作用方式。它似乎在长春花部位结合，但表现出一些与紫杉烷部位配体相似的性质，例如增强微管蛋白的聚合。该化合物可抵抗多种肿瘤，包括对紫杉醇和长春新碱有抗药性的肿瘤。此外，西维帕布林稳定且水溶性，可以在生理盐水中静脉内或口服给药。它可以有效地大量合成。基于这些特性，选择了Cevipabulin进行临床开发。但表现出一些与紫杉烷位配体相似的性质，例如增强微管蛋白聚合。该化合物可抵抗多种肿瘤，包括对紫杉醇和长春新碱有抗药性的肿瘤。此外，西维帕布林稳定且水溶性，可以在生理盐水中静脉内或口服给药。它可以有效地大量合成。基于这些特性，选择了Cevipabulin进行临床开发。但表现出一些与紫杉烷位配体相似的性质，例如增强微管蛋白聚合。该化合物可抵抗多种肿瘤，包括对紫杉醇和长春新碱有抗药性的肿瘤。此外，西维帕布林稳定且水溶性，可以在生理盐水中静脉内或口服给药。它可以有效地大量合成。基于这些特性，选择了Cevipabulin进行临床开发。