spindles

Ciliobrevin D 是细胞渗透性，可逆和特异性的 AAA + ATPase 运动细胞质动力蛋白抑制剂。它在体外抑制依赖于动力蛋白的微管滑动和 ATPase 活性。它抑制Hedgehog 信号和初级纤毛形成。

Phenytoin (5,5-Diphenylhydantoin) 是一种有效的电压门控钠离子通道阻滞剂，可减少小鼠乳腺肿瘤的生长和转移，具有抗癫痫活性。

Indibulin (D 24851) 是一种口服有效的微管蛋白合成抑制剂，具有抗有丝分裂和抗肿瘤活性，且神经毒性小。它降低了肌间神经张力，产生异常的纺锤体，激活有丝分裂检查点蛋白 Mad2 和 BubR1，并诱导有丝分裂停滞和细胞凋亡。

ER-076349 作为一种微管蛋白聚合抑制剂，不仅可以诱导 G2-M 细胞周期的停滞，还能破坏有丝分裂纺锤体。该化合物有效抑制癌细胞和多种人类肿瘤异种移植小鼠模型中肿瘤的生长。此外，ER-076349 是 Halichondrin B 的类似物。

Dimethylenastron 是一种驱动蛋白Eg5抑制剂，IC50值为 200 nM。它可阻止具有单极纺锤体的细胞，所有染色体都以单极纺锤体方式附着在该纺锤体上。

Microtubule stabilizing agent. Potent inhibitor of cellular proliferation in cancer cell lines (IC50 reported to be 3-30 nM, dependent on cell line used). Causes cells to arrest in the prometaphase of the cell cycle, prevents formation of bipolar spindle and increases kinetochore tension in preformed spindles. Pryor et al (2002) The microtubule stabilizing agent laulimalide does not bind in the taxoid site, kills cells resistant to PacT. and epothilones, and may not require its epoxide moiety for activity. Biochemistry. 41 9109 PMID:12119025 |Bennett et al (2012) Low-dose laulimalide represents a novel molecular probe for investigating microtubule organization. Cell Cycle. 11 3045 PMID:22871740 |Bennett et al (2010) Discovery and characterization of the laulimalide-microtubule binding mode by mass shift perturbation mapping. Chem.Biol. 17 725 PMID:20659685

4SC-207 is a novel microtubule inhibitor , which shows strong anti-proliferative activity in a large panel of tumor cell lines with an average GI50 of 11 nM. In particular, 4SC-207 is active in multi-drug resistant cell lines, such as HCT-15 and ACHN, suggesting that it is a poor substrate for drug efflux pumps. 4SC-207 inhibits microtubule growth in vitro and in vivo and promotes, in a dose dependent manner, a mitotic delay arrest, followed by apoptosis or aberrant divisions due to chromosome alignment defects and formation of multi-polar spindles. Furthermore, preliminary data from preclinical studies suggest low propensity towards bone marrow toxicities at concentrations that inhibit tumor growth in paclitaxel-resistant xenograft models. 4SC-207 may be a potential anti-cancer agent.

DAP-81 is a diaminopyrimidine derivative that targets PLKs, destabilizing kinetochore microtubules. Other spindle tubules are stabilized, resulting in monopolar mitotic spindles. In vitro, DAP-81 inhibits Plk1 at an IC50 of 0.9 nM. DAP-81 is currently in ongoing preclinical evaluations.

AZD4877 is a synthetic kinesin spindle protein (KSP) inhibitor with potential antineoplastic activity. KSP inhibitor AZD4877 selectively inhibits microtubule motor protein KSP (also called kinesin-5 or Eg5), which may result in the inhibition of mitotic spindle assembly; activation of the spindle assembly checkpoint; induction of cell cycle arrest during the mitotic phase; and cell death in tumor cells that are actively dividing. Because KSP is not involved in postmitotic processes, such as neuronal transport, this agent may be less likely to cause the peripheral neuropathy often associated with the tubulin-targeting agents. Eg5 is essential for the formation of bipolar spindles and the proper segregation of sister chromatids during mitosis.

DAT-230 is a promising microtubule inhibitor that has great potential for the treatment of fibrosarcoma in vitro and in vivo. DAT-230 exhibited potent anti-proliferative activity against various cancer cells. DAT-230 -treatment in HT-1080 cells resulted in microtubule de-polymerization and G2 M phase arrest preceding apoptosis. Phosphor-cdc2 (thr14 tyr15) reduction, cyclin B1 accumulation and aberrant spindles denoted the cyclin B1-cdc2 complex active and M phase arrest in HT-1080 cells treated with DAT-230. Apoptosis induced by DAT-230 was related with the activation of caspase-9, caspase-3 and PARP cleavage, which were at the downstream of mitochondria.

Solidagonic acid 通过促进异常单极纺锤体向双极纺锤体的转变来抑制 HSET 运动活动。Solidagonic acid 抑制裂殖酵母细胞死亡，并使有丝分裂纺锤体从单极形态逆转为双极形态。Solidagonic acid 对 Lactuca sativaL. 和 Lolium multiflorumLam 的幼苗具有生长抑制活性。