Ueda K, Banasik M, Nakajima S, Yook H Y, Kido T
Laboratory of Molecular Clinical Chemistry, Kyoto University, Japan.
Biochimie. 1995;77(5):368-73. doi: 10.1016/0300-9084(96)88148-x.
From a survey of about 400 compounds, we found a number of potent and specific inhibitors of poly(ADP-ribose) synthetase. Two new classes of inhibitors include vesnarinones and heterocyclic amines. Although the inhibitory activity was not very strong, several of these classes of inhibitors proved to induce most efficiently differentiation of murine teratocarcinoma EC cells in culture; for example, 70 microM benzylvesnarinone or 1 mM PhIP effected almost complete change in cell morphology in 5 to 7 days. Analyses of poly(ADP-ribose) synthesis and NAD concentrations in EC cells after treatment with a differentiation inducer suggested that poly(ADP-ribose) might play a role at an initiation stage of cell differentiation.
通过对约400种化合物的调查，我们发现了多种聚（ADP-核糖）合成酶的强效特异性抑制剂。两类新型抑制剂包括维司那定和杂环胺。尽管这些抑制剂的抑制活性不是很强，但其中几类抑制剂被证明能最有效地诱导培养的小鼠畸胎癌EC细胞分化；例如，70微摩尔的苄基维司那定或1毫摩尔的PhIP在5至7天内几乎使细胞形态完全改变。在用分化诱导剂处理EC细胞后，对聚（ADP-核糖）合成和NAD浓度的分析表明，聚（ADP-核糖）可能在细胞分化的起始阶段发挥作用。
