The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
ATP citrate lyase (ACLY) inhibitors: An anti-cancer strategy at the crossroads of glucose and lipid metabolism
Open accessAbstract
ATP citrate lyase (ACLY) is a cytosolic homotetrameric enzyme that catalyzes the conversion of citrate and coenzyme A (CoA) to acetyl-CoA and oxaloacetate, with the simultaneous hydrolysis of ATP to ADP and phosphate. Interestingly, ACLY is a strategic enzyme linking both the glycolytic and lipidic metabolism. In tumour cells characterized by an altered energetic metabolism, an increased glucose uptake and an accelerated glycolytic flux lead to an intensified production of mitochondrial citrate. Once transported to the cytosol, citrate is here converted by ACLY to acetyl-CoA, an essential biosynthetic precursor for fatty acid synthesis and mevalonate pathway. ACLY expression and activity proved to be aberrantly expressed in many types of tumours, and its pharmacological or genetic inhibition significantly inhibited cancer cell proliferation and induced apoptosis. Increasing evidences highlight the central role of ACLY, conferring a great therapeutic potential to this enzyme as a key target for the treatment of cancer. ACLY inhibitors, previously developed for metabolic disorders, have recently attracted interest as promising anti-cancer agents. After a brief introduction to the structure and the pathophysiological role of ACLY, this review article provides an overview of the main ACLY inhibitors reported in the literature.
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Cites
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Lipid metabolism in cancer: New perspectives and emerging mechanisms
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Lactate supports a metabolic-epigenetic link in macrophage polarization
Noe, J. T., Rendon, B. E., Geller, A. E., Conroy, L. R., Morrissey, S. M., Young, L. E. A., Bruntz, R. C., Kim, E. J., Wise-Mitchell, A., Barbosa de Souza Rizzo, M., et al. (2021) · Science Advances · doi:10.1126/sciadv.abi8602 · Cited by 283
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Metadata
- Authors
- Granchi, C.
- Venue
- European Journal of Medicinal Chemistry
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 157
- Pages
- 1276-1291
- ISSN
- 0223-5234 (ISSN-L)
- OpenAlex
- W2889204304
- Cited by
- 245
- References
- 10
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- green
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