Sawa Masaaki, Masai Hisao
Carna Biosciences Inc., Kobe, Japan.
Drug Des Devel Ther. 2009 Feb 6;2:255-64. doi: 10.2147/dddt.s4303.
Identification of novel molecular targets is critical in development of new and efficient cancer therapies. Kinases are one of the most common drug targets with a potential for cancer therapy. Cell cycle progression is regulated by a number of kinases, some of which are being developed to treat cancer. Cdc7 is a serine-threonine kinase originally discovered in budding yeast, which has been shown to be necessary to initiate the S phase. Inhibition of Cdc7 in cancer cells retards the progression of the S phase, accumulates DNA damage, and induces p53-independent cell death, but the same treatment in normal cells does not significantly affect of less than viability. Low-molecular-weight compounds that inhibit Cdc7 kinase with an IC(50) 10 nM have been identified, and shown to be effective in the inhibition of tumor growth in animal models. Thus Cdc7 kinase can be recognized as a novel molecular target for cancer therapy.
识别新的分子靶点对于开发新型高效的癌症治疗方法至关重要。激酶是最常见的药物靶点之一,具有癌症治疗潜力。细胞周期进程受多种激酶调控,其中一些激酶正被开发用于治疗癌症。Cdc7是一种最初在芽殖酵母中发现的丝氨酸 - 苏氨酸激酶,已证明它对启动S期是必需的。在癌细胞中抑制Cdc7会延缓S期进程,积累DNA损伤,并诱导不依赖p53的细胞死亡,但对正常细胞进行相同处理不会显著影响其活力或仅有轻微影响。已鉴定出抑制Cdc7激酶的IC(50)为10 nM的低分子量化合物,并证明其在动物模型中对抑制肿瘤生长有效。因此,Cdc7激酶可被视为癌症治疗的新分子靶点。