Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
Clin Cancer Res. 2011 Jun 1;17(11):3527-32. doi: 10.1158/1078-0432.CCR-10-2504. Epub 2011 Mar 8.
The big mitogen activated protein kinase 1 (BMK1) pathway is the most recently discovered and least-studied mammalian mitogen-activated protein (MAP) kinase cascade, ubiquitously expressed in all types of cancer cells tested so far. Mitogens and oncogenic signals strongly activate this cellular MAP kinase pathway, thereby passing down proliferative, survival, chemoresistance, invasive, and angiogenic signals in tumor cells. Recently, several pharmacologic small molecule inhibitors of this pathway have been developed. Among them, the BMK1 inhibitor XMD8-92 blocks cellular BMK1 activation and significantly suppresses tumor growth in lung and cervical tumor models and is well tolerated in animals. On the other hand, MEK5 inhibitors, BIX02188, BIX02189, and compound 6, suppress cellular MEK5 activity, but no data exist to date on their effectiveness in animals.
大丝裂原活化蛋白激酶 1（BMK1）途径是最近发现的、研究最少的哺乳动物丝裂原活化蛋白（MAP）激酶级联反应，迄今为止在所有测试的癌症细胞类型中均广泛表达。有丝分裂原和致癌信号强烈激活该细胞 MAP 激酶途径，从而将增殖、存活、化疗耐药性、侵袭性和血管生成信号传递到肿瘤细胞中。最近，已经开发出几种该途径的药理学小分子抑制剂。其中，BMK1 抑制剂 XMD8-92 阻断细胞 BMK1 激活，并显著抑制肺癌和宫颈癌模型中的肿瘤生长，且在动物中具有良好的耐受性。另一方面，MEK5 抑制剂 BIX02188、BIX02189 和化合物 6 抑制细胞 MEK5 活性，但迄今为止尚无其在动物中的有效性数据。
