癌干细胞（CSCs）是癌症治疗中相关的治疗靶点。尽管如此，CSC特征的分子回路尚未完全理解。CSC数量较少有时会阻碍对其特性进行探索性实验。因此，通过小分子介导的细胞重编程来增加CSC数量似乎是一种有效的替代工具。我们使用嵌入在胃非CSCs（SORE6-）中的SORE6-GFP报告系统，在1200种小分子中进行了高通量的基于图像的药物筛选，以找出能够将SORE6-转化为SORE6+（CSCs）的化合物。在这里，我们报告了抗真菌剂环氧嗪醇胺（CPX）的药物再利用作为癌症治疗的潜在候选药物，能够通过激活SOX2表达和增加C-MYC、HIF-1α、KLF4和HMGA1的表达，将胃非CSCs重编程为癌症干细胞样细胞。这种重编程依赖于CPX的浓度和处理时间。CPX还可以诱导细胞衰老和从氧化磷酸化（OXPHOS）转变为糖酵解的代谢转变。我们还披露了细胞重编程的机制与钴氯化物（CoCl2），一种模拟缺氧的药物，类似。

Cancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC numbers via small molecule-mediated cellular reprogramming appears to be a valid alternative tool. Using the SORE6-GFP reporter system embedded in gastric non-CSCs (SORE6-), we performed a high-throughput image-based drug screen with 1200 small molecules to identify compounds capable of converting SORE6- to SORE6+ (CSCs). Here, we report that the antifungal agent ciclopirox olamine (CPX), a potential candidate for drug repurposing in cancer treatment, is able to reprogram gastric non-CSCs into cancer stem-like cells via activation of SOX2 expression and increased expression of C-MYC, HIF-1α, KLF4, and HMGA1. This reprogramming depends on the CPX concentration and treatment duration. CPX can also induce cellular senescence and the metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis. We also disclose that the mechanism underlying the cellular reprogramming is similar to that of cobalt chloride (CoCl2), a hypoxia-mimetic agent.