尽管新型抗癌药物取得了一些进展，但约60%至80%的完全缓解患者在常规化疗后最终会复发，并且预后较差。因此，持续开发更有效的新型治疗急性髓性白血病(AML)非常必要。我们开发了(R)-WAC-224(R-WAC)，这是一种靶向DNA酶II的抗癌喹诺酮。本研究在体外和体内评估了R-WAC或外消旋WAC-224(WAC)的抗白血病潜力。R-WAC明显抑制了人AML细胞系(MV4-11、HL60和KG1a)的增殖，这与多柔比星和阿糖胞苷相似，并不受P-糖蛋白过表达的影响。WAC既不增加血清肌钙蛋白T也不降低小肠的隐窝数，表明WAC的毒性比阿霉素小。R-WAC单药疗法延长了AML小鼠模型的存活期，并抑制了MV4-11异种移植小鼠模型的肿瘤生长。此外，R-WAC与阿糖胞苷联合治疗比多柔比星和阿糖胞苷更具活性的抗白血病效果。最后，R-WAC抑制了原发AML细胞的集落形成能力。这些结果表明，R-WAC是AML的一种有希望的治疗药物。© 2023. 作者通过独家许可授予Springer Science+Business Media, LLC，属于Springer Nature。

Approximately 60%-80% of patients who achieve complete remission eventually relapse after conventional chemotherapy and have poor prognoses despite the recent advances of novel anticancer agents. Continuing development of more effective novel treatments for acute myeloid leukemia (AML) is necessary. We developed (R)-WAC-224 (R-WAC), which is an anticancer quinolone, targeting topoisomerase II. This study evaluated the anti-leukemia potential of R-WAC or racemic WAC-224 (WAC) in vitro and in vivo. R-WAC significantly inhibited the human AML cell line proliferation (MV4-11, HL60, and KG1a), which was comparable to daunorubicin and cytarabine, not affected by P-glycoprotein overexpression. WAC did neither increase serum troponin-T nor decrease the crypt numbers in the small intestine, indicating WAC was less toxic than doxorubicin. R-WAC monotherapy demonstrated prolonged survival in the AML mice model and inhibited tumor growth in the MV4-11 xenograft mice model. Moreover, the combination of R-WAC and cytarabine demonstrated more active anti-leukemia effects than daunorubicin and cytarabine. Finally, R-WAC inhibited the colony-forming abilities using primary AML cells. These results indicate that R-WAC is a promising therapeutic agent for AML.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.