2. Academic Validation
  3. A Cyclometalated Iridium(III) Complex Exerts High Anticancer Efficacy via Fatty Acid Beta-Oxidation Inhibition and Sphingolipid Metabolism Reprogramming

A Cyclometalated Iridium(III) Complex Exerts High Anticancer Efficacy via Fatty Acid Beta-Oxidation Inhibition and Sphingolipid Metabolism Reprogramming

  • J Med Chem. 2024 Sep 12;67(17):14912-14926. doi: 10.1021/acs.jmedchem.4c00280.
Cuiyan Lin 1 2,  Huiling Wang 1 2,  Keyu Chen 2,  Shuangqiang Liu 2,  Zhichen Mao 2,  Zuyu Mo 2 3,  Rizhen Huang 2,  Ye Zhang 2,  Wei Xie 4,  Jianhua Wei 1 4 2 3,  Junfei Jin 1 4 5 6 7
Affiliations

Affiliations

  • 1 Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, China.
  • 2 Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, Key Laboratory of Medical Biotechnology and Translational Medicine, School of Pharmacy, Guilin Medical University, Guilin, Guangxi 541199, China.
  • 3 State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Centre for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
  • 4 Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210096, China.
  • 5 Guangxi Health Commission Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, China.
  • 6 China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, Guangxi 541001, China.
  • 7 Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, China.
PMID: 39226239 DOI: 10.1021/acs.jmedchem.4c00280
Abstract

Given the extensive role of lipids in Cancer development, there is substantial clinical interest in developing therapies that target lipid metabolism. In this study, we identified one cyclometalated iridium complex (Ir2) that exhibits potent antiproliferation activity in MIA PaCa-2 cells by regulating fatty acid metabolism and sphingolipid metabolism simultaneously. Ir2 also efficiently overcomes cisplatin resistance in vitro. Satisfyingly, the generated Ir2@F127 carriers, as a temperature-sensitive in situ gelling system of Ir2, showed effective Cancer treatment with minimal side effects in an in vivo xenograft study. To the best of our knowledge, Ir2 is the first reported cyclometalated iridium complex that exerts Anticancer activity in MIA PaCa-2 cells by intervening in lipid metabolism, which provides an alternative pathway for the Anticancer mechanism of cyclometalated iridium complexes.

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