Day C E, Schurr P E, Phillips W A
Adv Exp Med Biol. 1978;109:277-83. doi: 10.1007/978-1-4684-0967-3_15.
We have developed an integrated system for antiatherosclerosis drug development utilizing rats, SEA quail, and cynomolgus monkeys as animal models. In general, the way the system is presently functioning is that thousands of compounds per year are randomly screened for hypobeta- or hyperalphalipoproteinemic activity in rats, and hundreds of compounds per year are screened in SEA quail for antiatherosclerotic and hypocholesterolaric activity. A few selected compounds that have activity in both rats and quail are then tested for lipoprotein modifying activity in cynomolgus monkeys. Nontoxic compounds having very good lipoprotein modifying activity in the monkey will then be recommended for clinical trials in man. We do not anticipate that this battery of testing will guarantee activity in man, but are hoping that it will at least increase the probability for finding a truly effective antiatherosclerotic drug to control the human disease.
我们已经开发了一个用于抗动脉粥样硬化药物研发的综合系统，该系统利用大鼠、日本鹌鹑和食蟹猴作为动物模型。一般来说，该系统目前的运作方式是，每年在大鼠中对数千种化合物进行随机筛选，以检测其低β脂蛋白血症或高α脂蛋白血症活性，每年在日本鹌鹑中筛选数百种化合物，以检测其抗动脉粥样硬化和降胆固醇活性。然后，对在大鼠和鹌鹑中均具有活性的少数选定化合物进行食蟹猴脂蛋白修饰活性测试。在猴子中具有非常好的脂蛋白修饰活性的无毒化合物将被推荐用于人体临床试验。我们预计这一系列测试不能保证在人体中具有活性，但希望它至少能增加找到一种真正有效的抗动脉粥样硬化药物来控制人类疾病的概率。
