2. Academic Validation
  3. Targeting Colorectal Cancer with Conjugates of a Glucose Transporter Inhibitor and 5-Fluorouracil

Targeting Colorectal Cancer with Conjugates of a Glucose Transporter Inhibitor and 5-Fluorouracil

  • J Med Chem. 2021 Apr 22;64(8):4450-4461. doi: 10.1021/acs.jmedchem.0c00897.
Chun-Kai Chang 1,  Pei-Fang Chiu 1,  Hui-Yi Yang 1,  Yu-Pu Juang 1,  Yen-Hsun Lai 1,  Tzung-Sheng Lin 1,  Lih-Ching Hsu 1,  Linda Chia-Hui Yu 2,  Pi-Hui Liang 1 3
Affiliations

Affiliations

  • 1 School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
  • 2 Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
  • 3 The Genomics Research Center, Academia Sinica, Taipei 128, Taiwan.
PMID: 33819035 DOI: 10.1021/acs.jmedchem.0c00897
Abstract

Overexpression of glucose transporters (GLUTs) in colorectal Cancer cells is associated with 5-fluorouracil (1, 5-FU) resistance and poor clinical outcomes. We designed and synthesized a novel GLUT-targeting drug conjugate, triggered by glutathione in the tumor microenvironment, that releases 5-FU and GLUTs inhibitor (phlorizin (2) and phloretin (3)). Using an orthotopic colorectal Cancer mice model, we showed that the conjugate exhibited better antitumor efficacy than 5-FU, with much lower exposure of 5-FU during treatment and without significant side effects. Our study establishes a GLUT-targeting theranostic incorporating a disulfide linker between the targeting module and cytotoxic payload as a potential antitumor therapy.

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