共查询到16条相似文献,搜索用时 62 毫秒
1.
2.
3.
4.
5.
Aurora激酶抑制剂研究进展 总被引:2,自引:1,他引:2
Aurora激酶家族是细胞有丝分裂期重要的调节因子,可影响细胞周期进程,是抗肿瘤药物的新靶点。简述Aurora激酶的生物学和与肿瘤发生发展的关系,重点介绍Aurora激酶抑制剂的结构类型和构效关系。 相似文献
6.
酪氨酸激酶介导的信号转导与肿瘤发生发展直接相关,针对这一途径研发药物已成为当前抗肿瘤治疗的热点,并且取得了重要进展.该文综述酪氨酸激酶的作用机制、酪氨酸激酶抑制剂的临床应用现状及其存在的问题. 相似文献
7.
目的综述有丝分裂关键激酶抑制剂近年来的研究进展。方法根据已报道的有丝分裂中关键激酶抑制剂的文献,将对有丝分裂过程中与肿瘤发生联系密切的激酶抑制剂,如Aurora激酶抑制剂、CDK(cyclin-dependent kinase)激酶抑制剂、PLK(Polo-like kinase)激酶抑制剂、CHK(check-point kinase)激酶抑制剂等目前的研究进展进行综述。结果有丝分裂关键激酶抑制剂已在临床前研究及临床研究中显示出很好的抗肿瘤活性。结论随着研究的不断深入,有丝分裂关键激酶抑制剂将在肿瘤治疗中发挥更大的作用。 相似文献
8.
目的综述蛋白酪氨酸激酶(protein tyrosine kinase,PTK)抑制剂类抗肿瘤药物的研究进展。方法根据已报道的PTK抑制剂的相关文献,将其分为国外已经上市、国外处于临床研究和我国自主研发的PTK抑制剂进行具体介绍。结果 PTK在细胞内的信号转导中起着重要的作用,与肿瘤细胞的生长、增殖、分化和凋亡密切相关,目前已经有多种结构的PTK抑制剂类抗肿瘤药物上市或进入临床研究。结论随着PTK的作用机制及构效关系研究的不断深入,该类药物终将成为治疗肿瘤的有效药物。 相似文献
9.
目的:MTT法分析Aurora激酶抑制剂,vx-680,对细胞株TSCCa,Tca8113,KB,CNE2生长增殖的影响。方法不同浓度的vx-680作用TSCCa,Tca8113,KB,CNE224h后MTT法检测细胞株TSCCa,Tca8113,KB,CNE2生长增殖情况,计算半数抑制浓度。结果vx-680效抑制TSCCa,Tca8113,KB,CNE2细胞株增殖,半数抑制浓度分别为8.78,6.53,3.35,6.93nM。结论初次阐述Aurora激酶抑制剂在体外可以有效抑制头颈肿瘤细胞的生长增殖的影响。 相似文献
10.
蛋白酪氨酸激酶(PTK)抑制剂是一类作用于细胞信号转导通路的分子靶向药物,针对特定靶点发挥抗肿瘤作用。目前已有十余种蛋白酪氨酸激酶抑制剂上市,且它们在多种实体瘤的治疗中显示出较好的疗效。该文对近年来蛋白酪氨酸激酶抑制剂的研究进展做简要综述。 相似文献
11.
MM NEAZ M MUDDASSAR FA PASHA Seung Joo CHO 《Acta pharmacologica Sinica》2010,31(2):244-258
Aim:
To characterize the structural features of quinazoline-based Aurora B inhibitors that influence its inhibitor activity.Methods:
Two geometrical methods, Method 1 and Method 2, were used to develop the 3D-QSAR models. The most active ligand was used as the template for the alignment of all the ligands in Method 1, and a conformer of the cocrystal ligand was used as the template for the alignment of all the ligands in Method 2.Results:
The models suggest that highly active ligands can be designed by varying the R1 substituent at position 7 of the quinazoline ring with positively charged, bulky, hydrophobic groups, while bulky and hydrophobic groups around the thiazole ring are desirable for higher activity.Conclusion:
This study emphasizes that the bioactive conformer is rather different from the minima. The steric, electrostatic, and hydrophobic field effects contribute to its inhibitory activity. 相似文献12.
《Expert opinion on therapeutic targets》2013,17(12):1377-1393
Introduction: Aurora proteins are serine/threonine kinases with critical functions during mitosis. Aurora A, one of the members of this family, participates in crucial processes including mitotic entry, DNA damage checkpoint recovery and centrosome and spindle maturation. Aurora A is frequently overexpressed in human cancers and, when inhibited, impairs cell proliferation.Areas covered: Here, we review the preclinical studies that support the use of Aurora A inhibitors in antitumoral strategies. We also discuss past or current clinical trials using Aurora A inhibitors in multiple tumor types. We pay special attention to Alisertib, a potent and selective Aurora A inhibitor currently in Phase III.Expert opinion: The potential of Aurora A inhibitors in the treatment of cancer depends on many factors, mainly related with the molecular status of tumor cells. Yet, we still need to find proper biomarkers to select those patients that better react to Aurora A inhibitors. Furthermore, their effect could significantly improve when used in combination with other drugs. Although some clinical trials are already testing the cooperative effect of different antitumoral drugs, additional preclinical studies are necessary to establish the best combinations. Here, we discuss some possibilities that could be explored in future studies. 相似文献
13.
目的 从结构出发介绍Aurora激酶及其抑制剂的研究进展。方法 总结 Aurora激酶抑制剂骨架特征和结合模式,以及进入临床的Aurora激酶抑制剂的研究进展。结果和结论 Aurora激酶家族是肿瘤治疗的一个新兴靶标。腺嘌呤骨架可能是设计高活性Aurora激酶抑制剂的重要母核。 相似文献
14.
15.
16.
An update on the pharmacokinetics and pharmacodynamics of alisertib,a selective Aurora kinase A inhibitor
下载免费PDF全文
![点击此处可从《Clinical and experimental pharmacology & physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Cameron T Durlacher Zhi‐Ling Li Xiao‐Wu Chen Zhi‐Xu He Shu‐Feng Zhou 《Clinical and experimental pharmacology & physiology》2016,43(6):585-601
Human Aurora kinases, including Aurora kinase A (AURKA), B (AURKB), and C (AURKC), play an essential role in mitotic events such as monitoring of the mitotic checkpoint, creation of bipolar mitotic spindle and alignment of centrosomes on it, also regulating centrosome separation, bio‐orientation of chromosomes and cytokinesis. AURKA and AURKB are key regulators of mitosis and centrosome via polymerizing microfilaments and controlling chromatid segregation. In particular, AURKA plays critical roles in the regulation of mitotic entry, centrosome function, bipolar spindle assembly, and chromosome segregation. AURKA has been found to be overexpressed in various solid and haematological cancers and has been linked with poor prognosis. Its important role in cancer initiation, growth, and metastasis has brought the focus to search for potent and selective AURKA inhibitors for cancer treatment. MLN8237, also known as alisertib, is one selective AURKA inhibitor that has shown remarkable anticancer effects in preclinical studies. Alisertib exhibits favourable pharmacokinetic properties. Alisertib has generally showed good partial response rates of 4–52% and good safety profiles in Phase I and II trials when it is solely administered as well as combined with cytotoxic chemotherapeutic drugs. Recently, the multicentre, randomized Phase III study of alisertib in patients with relapsed or refractory peripheral T‐cell lymphoma has been discontinued due to unsatisfactory efficacy. The low risk of side effects, accessibility, and effectiveness of alisertib makes it a new promising anticancer therapy and further mechanistic and clinical studies are warranted. 相似文献