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  3. The fluoroquinoline compound exerts anti-erythroleukemic effects by dual-targeting GLUT1 and the PI3K/AKT signaling pathway

The fluoroquinoline compound exerts anti-erythroleukemic effects by dual-targeting GLUT1 and the PI3K/AKT signaling pathway

  • Sci Rep. 2026 Mar 27;16(1):10916. doi: 10.1038/s41598-026-45597-9.
Sha Cheng # 1 2,  Weijia Zhao # 1 2,  Jia Yu 1 2,  Xueling Meng 1 2,  Bixue Xu 1 2,  Ningning Zan 3 4,  Baofei Sun 5 6,  Heng Luo 7 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, Guizhou, China.
  • 2 Natural Products Research Center of Guizhou Province, Guiyang, 550014, Guizhou, China.
  • 3 State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, Guizhou, China. zan11658@163.com.
  • 4 Natural Products Research Center of Guizhou Province, Guiyang, 550014, Guizhou, China. zan11658@163.com.
  • 5 State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, Guizhou, China. 1589894559@qq.com.
  • 6 Natural Products Research Center of Guizhou Province, Guiyang, 550014, Guizhou, China. 1589894559@qq.com.
  • 7 State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, Guizhou, China. luoheng71050@aliyun.com.
  • 8 Natural Products Research Center of Guizhou Province, Guiyang, 550014, Guizhou, China. luoheng71050@aliyun.com.
  • # Contributed equally.
PMID: 41896383 DOI: 10.1038/s41598-026-45597-9
Abstract

Erythroleukemia is a rare hematological malignancy in clinical practice, and currently, there are no effective treatment options Other than stem cell transplantation. The study found that the fluoroquinoline compound FKL-137 can significantly inhibit the proliferation of erythroleukemia cells and induce Apoptosis in vitro, while in vivo, it prevents the development of Friend virus-induced erythroleukemia and splenomegaly in mice. Mechanistic studies revealed that FKL-137 reduces glucose uptake and lactate secretion in erythroleukemia cells by targeting GLUT1 and inhibits the expression of glucose metabolism-related proteins, including PKM2, HK2, and LDH. Additionally, FKL-137 modulates the PI3K/Akt signaling pathway, which is closely associated with GLUT1. These results highlight the critical role of GLUT1 in the growth and survival of erythroleukemia and demonstrate that FKL-137 exerts its regulatory effects on glucose metabolism through the dual-targeting of GLUT1 and the PI3K/Akt signaling pathway, making it a potential therapeutic agent for erythroleukemia.

Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-026-45597-9.

Keywords

Erythroleukemia; Fluoroquinoline; GLUT1; Glucose metabolism; Glycolysis; PI3K/AKT.

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