Small molecules that regulate cell stemness have the potential to make a major contribution to regenerative medicine. In the course of screening for small molecules that affect stemness in mouse embryonic stem cells (mESCs), we discovered that NPD13432, an aurone derivative, promoted self-renewal of mESCs. Normally, mESCs start to differentiate upon withdrawal of 2i/LIF. However, cells treated with the compound continued to express endogenous Nanog, a pluripotency marker protein essential for sustaining the undifferentiated state, even in the absence of 2i/LIF. Biochemical characterization revealed that NPD13432 inhibited GSK3α and GSK3β with IC₅₀ values of 92 nM and 310 nM, respectively, suggesting that the compound promotes self-renewal in mESCs by inhibiting GSK3. The chemical structure of the compound is unique among known molecules with this activity, providing an opportunity to develop new inhibitors of GSK3, as well as chemical tools for investigating cell stemness.

调节细胞干性的小分子有可能对再生医学做出重大贡献。在筛选影响小鼠胚胎干细胞（mESCs）干性的小分子的过程中，我们发现NPD13432（一种金黄色素衍生物）促进了mESCs的自我更新。通常，在退出2i / LIF时，mESC开始分化。但是，用该化合物处理的细胞继续表达内源性Nanog，这是一种即使在没有2i / LIF的情况下也能维持未分化状态所必需的多能性标记蛋白。生化特征表明，NPD13432通过IC ₅₀抑制GSK3α和GSK3β值分别为92 nM和310 nM，表明该化合物通过抑制GSK3促进mESCs的自我更新。该化合物的化学结构在具有这种活性的已知分子中是独特的，为开发新的GSK3抑制剂以及研究细胞干性的化学工具提供了机会。