多形性胶质母细胞瘤（GBM）是最致命的脑肿瘤，有效的治疗方案仍然难以捉摸。目前的最大切除随后化疗的治疗程序已被证明严重不足以防止疾病进展和死亡。尽管尽了最大努力，诊断后的最长生存期仅为 1.5 年。因此，寻找有效的治疗方法来预防GBM的发病和复发存在巨大的未满足的临床需求。信号通路的小分子抑制剂是预防各种类型肿瘤的一个有吸引力的选择。然而，目前还没有有效的小分子抑制剂在临床试验中成功对抗 GBM。 GBM 的发病机制涉及多种信号传导途径的改变，以及一系列信号分子、转录因子 (TF) 和表观遗传修饰因子。 JAK-STAT 通路改变是 GBM 发病机制和复发的重要因素。许多 JAK 或 STAT TF 的小分子抑制剂，特别是 JAK2 和 STAT3，已被评估其在 GBM 中的抗肿瘤活性。然而，迄今为止尚未取得明确的成功。在此，通过使用两种JAK3小分子抑制剂，我们发现它们在抑制GBM细胞增殖和神经球形成、下调其干性特征以及诱导分化为神经元起源细胞方面非常有效。无论是在含血清的分化培养基中还是在含有 EGF 和 FGF 的增殖培养基中，使用这些药物进行单次治疗在限制 GBM 细胞生长方面都非常有效，这表明这些 JAK 抑制剂在 GBM 治疗中具有潜在的治疗应用。

Glioblastoma multiforme (GBM) is the most deadly brain tumor, effective treatment options for which still remain elusive. The current treatment procedure of maximal resection followed by chemotherapy has proved to be grossly insufficient to prevent disease progression and death. Despite best efforts, the maximum survival post-diagnosis is a mere 1.5 years. Therefore, there is a huge unmet clinical need to find effective therapeutic procedures to prevent the pathogenesis and relapse of GBM. Small-molecule inhibitors of signaling pathways are an attractive option to prevent various types of tumors. However, no effective small-molecule inhibitors have been successful against GBM in clinical trials. Various signaling pathways are altered and an array of signaling molecules, transcription factors (TFs), and epigenetic modifying factors have been implicated in the pathogenesis of GBM. JAK-STAT pathway alteration is an important contributor to GBM pathogenesis and relapse. Many small-molecule inhibitors of JAKs, or STAT TFs, especially JAK2 and STAT3, have been assessed for their anti-tumor activity in GBM. However, no definitive success so far has been achieved. Herein, by using two small-molecule inhibitors of JAK3, we show that they are quite effective in inhibiting GBM cell proliferation and neurosphere formation, downregulating their stemness character, and inducing differentiation into neuronal origin cells. The effect of a single treatment with the drugs, both in a serum-containing differentiation medium and in a proliferation medium containing EGF and FGF, was really strong in limiting GBM cell growth, suggesting a potential therapeutic application for these JAK inhibitors in GBM therapy.