Specific and nongenetic IAP-dependent Protein Erasers (SNIPERs) are a kind of PROTACs recruiting IAP ubiquitin ligases to induce degradation of target proteins. We have developed a series of SNIPERs against BCR-ABL oncogenic kinases by employing kinase inhibitors as target ligands. Some of these SNIPERs show potent activities to degrade BCR-ABL protein and inhibit CML cell growth. However, since SNIPERs also inhibit kinase activity, it takes some ingenuity to show that degradation of BCR-ABL plays a significant role on growth inhibitory activity. Here we describe protocols for synthesizing SNIPERs against BCR-ABL oncogenic kinase that contain kinase inhibitors as target ligands, and methods for evaluating the growth inhibitory activity against cancer cells, especially focusing on a method to discriminate the significance of protein degradation from that of kinase inhibition.

中文翻译：

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使用激酶抑制剂合成针对 BCR-ABL 的 SNIPER 以及评估其源自 BCR-ABL 降解的生长抑制活性的方法。

特定的和非遗传的 IAP 依赖性蛋白擦除器 (SNIPER) 是一种 PROTAC，它招募 IAP 泛素连接酶来诱导靶蛋白的降解。我们通过使用激酶抑制剂作为靶配体开发了一系列针对 BCR-ABL 致癌激酶的 SNIPER。其中一些 SNIPER 显示出强大的活性，可以降解 BCR-ABL 蛋白并抑制 CML 细胞生长。然而，由于 SNIPER 也会抑制激酶活性，因此需要一些独创性来表明 BCR-ABL 的降解对生长抑制活性起着重要作用。在这里，我们描述了针对包含激酶抑制剂作为靶配体的 BCR-ABL 致癌激酶合成 SNIPER 的方案，以及评估对癌细胞的生长抑制活性的方法，