Signal transducers and activators of transcription 5A and 5B (STAT5A and STAT5B) are two closely related STAT family members that are crucial downstream effectors of tyrosine kinase oncoproteins such as FLT3‐ITD in acute myeloid leukemia (AML) and BCR‐ABL in chronic myeloid leukemia (CML). We recently developed and reported the synthesis of a first molecule called 17 f that selectively inhibits STAT5 signaling in myeloid leukemia cells and overcomes their resistance to chemotherapeutic agents. To improve the antileukemic effect of 17 f, we synthesized ten analogs of this molecule and analyzed their impact on cell growth, survival, chemoresistance and STAT5 signaling. Two compounds, 7 a and 7 a’, were identified as having similar or higher antileukemic effects in various AML and CML cell lines. Both molecules were found to be more effective than 17 f at inhibiting STAT5 activity/expression and suppressing the chemoresistance of CML.

中文翻译：

---

靶向髓系白血病中 STAT5 信号传导的抑制剂：具有改善抗白血病潜力的新型四氢喹啉衍生物

信号转导和转录激活因子 5A 和 5B（STAT5A 和 STAT5B）是两个密切相关的 STAT 家族成员，它们是酪氨酸激酶癌蛋白（如急性髓性白血病 (AML) 中的 FLT3-ITD 和慢性髓性白血病中的 BCR-ABL）的关键下游效应器(CML)。我们最近开发并报告了第一个称为17 f 的分子的合成，该分子选择性地抑制髓系白血病细胞中的 STAT5 信号传导并克服它们对化学治疗剂的抗性。为了提高17 f的抗白血病作用，我们合成了该分子的十种类似物，并分析了它们对细胞生长、存活、化学抗性和 STAT5 信号传导的影响。两种化合物，7 a和7 a', 被确定为在各种 AML 和 CML 细胞系中具有相似或更高的抗白血病作用。发现这两种分子在抑制 STAT5 活性/表达和抑制 CML 的化学抗性方面比17 f更有效。