We report on the synthesis and in vitro biological evaluations of a nanomolar protein kinase inhibitor (PKI) and its β-glucuronidase-responsive albumin-binding prodrug. The highly potent PKI is 400–3400 times more cytotoxic than the well-known PKI Roscovitine. The prodrug is able to bind covalently to human serum albumin through Michael addition and release the cytotoxic PKI in the presence of β-glucuronidase, an enzyme over-expressed in the microenvironment of solid tumours.

中文翻译：

---

β-葡萄糖醛酸苷酸酶反应性白蛋白结合前药，用于潜在的基于选择性激酶抑制剂的癌症化疗

我们报告了纳摩尔蛋白激酶抑制剂（PKI）及其β-葡萄糖醛酸苷酶反应性白蛋白结合前药的合成和体外生物学评价。高效的PKI的细胞毒性是著名的PKI Roscovitine的400-3400倍。该前药能够通过迈克尔加成与人血清白蛋白共价结合，并在存在于实体瘤微环境中过表达的β-葡萄糖醛酸苷酶的情况下释放细胞毒性PKI。