期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 64, 期 8, 页码 4450-4461出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.0c00897
关键词
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资金
- Ministry of Science and Technology [MOST 108-3114-Y-001-002, 107-2320-B-002-019-MY3, 106-2320-B-002-017, 104-2320-B-002-008-MY3]
- Academia Sinica [AS-SUMMIT-109]
The study demonstrates that a novel GLUTs-targeting drug conjugate shows better antitumor efficacy than 5-FU in an orthotopic colorectal cancer mice model, with lower exposure of 5-FU during treatment and no significant side effects. This suggests that GLUT-targeting theranostics with a disulfide linker may be a promising approach for antitumor therapy.
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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