New opportunities to advance small-molecule kinase ligands that downregulate their cognate target binding proteins are discussed. Rationally designed heterobifunctional kinase degraders are compared with ATP site ligands that were serendipitously found to cause kinase downregulation. These approaches could be particularly useful in the treatment of cancers since many kinases are known to remodel pro-oncogenic protein-protein interactions, which could be destroyed by small-molecule-mediated kinase depletion.

中文翻译：

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小分子激酶下调剂

讨论了促进下调其同源靶结合蛋白的小分子激酶配体的新机会。将合理设计的异双功能激酶降解剂与偶然发现会导致激酶下调的ATP位点配体进行比较。这些方法在癌症的治疗中可能特别有用，因为已知许多激酶可以重塑致癌蛋白之间的相互作用，而这种相互作用可能会被小分子介导的激酶耗竭所破坏。