O6-甲基鸟嘌呤-DNA 甲基转移酶 (MGMT) 是一种 DNA 修复酶，在某些肿瘤中过度表达，并与 DNA 烷化剂替莫唑胺的耐药性相关。 MGMT 抑制剂显示出对抗替莫唑胺耐药性的潜力，但目前对 MGMT 酶活性和抑制作用的测定（主要基于寡核苷酸和荧光探针）既费力又昂贵。替莫唑胺治疗的临床意义需要更方便的方法来研究 MGMT 抑制。在这里，我们扩展了 SNAP-Capture 磁珠的应用，开发了一种新型 MGMT 抑制测定，该测定不仅对已知的 MGMT 抑制剂有效，而且对乙醛脱氢酶抑制剂双硫仑也有效。该测定使用标准荧光显微镜作为一种简单可靠的检测方法，并且可转化应用于药物发现项目。

O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that is overexpressed in certain tumors and is associated with resistance to the DNA alkylating agent temozolomide. MGMT inhibitors show potential in combating temozolomide resistance, but current assays for MGMT enzyme activity and inhibition, primarily oligonucleotide-based and fluorescent probe-based, are laborious and costly. The clinical relevance of temozolomide therapy calls for more convenient methodologies to study MGMT inhibition. Here, we extended the application of SNAP-Capture magnetic beads to develop a novel MGMT inhibition assay that demonstrated efficacy not only with known MGMT inhibitors, but also with the aldehyde dehydrogenase inhibitor, disulfiram. The assay uses standard fluorescence microscopy as a simple and reliable detection method, and is translationally applicable in drug discovery programs.