Progress of potential drugs targeted in lipid metabolism research

Liang, Kai; Dai, Jianye

doi:10.3389/fphar.2022.1067652

Cited by 14 publications

(4 citation statements)

References 204 publications

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“…The compound disrupts citrate binding and recognition by inducing conformational changes in the citrate domain. This allosteric inhibition underscores the potential of the allosteric site as a promising target in drug discovery, enhancing the likelihood of ACLY inhibitors (Jha et al, 2021;K. Liang & Dai, 2022;P.…”

Section: Ndi-091143mentioning

confidence: 83%

ATP-Citrate Lyase (ACLY): An Extensive Investigation from Molecular Insight to Therapeutic implications

Biju,

Chennam Lakshmikumar,

Rengasamy

2024

NRFHH

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ATP Citrate Lyase (ACLY) is a central enzyme bridging carbohydrate metabolism and lipid biosynthesis, crucial for various physiological processes and implicated in numerous pathologies. This review comprehensively describes ACLY, a pivotal enzyme at lipid biosynthesis and cellular metabolism interface. It serves as crucial role for several physiological functions, making it a highly valued topic for research. Starting with a description of the biochemistry and molecular biology of ACLY, elucidating its structural features, functions, and regulatory mechanisms, particularly in lipid synthesis and histone acetylation. Considering the pathophysiological aspect, the review also examines the relationship between ACLY dysregulation and associated diseases, explaining its contribution to pathological conditions mechanistically. An explanation of ACLY inhibitors is as follows: an overview of these inhibitors, an understanding of their mechanisms of action, and an analysis of their effectiveness and specificity. The following sections transition from preclinical studies, summarising key findings and knowledge into therapeutic potential, to clinical trials. The review offers updated information about ACLY research, integrating data from multiple sources to give an in-depth understanding. It concludes with the challenges and outlook facing the developing ACLY inhibitors, considering the strategies to overcome these challenges and the upcoming path in research and development in this promising field. This comprehensive examination not only encapsulates the knowledge at present but also aims to inspire and guide future inquiries into the complex realm of ACLY and its potential as a therapeutic target, ultimately improving patient outcomes and quality of life.

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Section: Ndi-091143mentioning

confidence: 83%

ATP-Citrate Lyase (ACLY): An Extensive Investigation from Molecular Insight to Therapeutic implications

Biju,

Chennam Lakshmikumar,

Rengasamy

2024

NRFHH

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“…Recently, there has been a growing interest in targeting key players in lipid metabolism as potential therapeutic approaches for managing lipid metabolism in disease. [ 64 ] It is to note that conventional drug effects typically do not exhibit tissue specificity and lack a circadian perspective. Therefore, future developments of drugs regulating lipid metabolism with consideration of targeted tissue and circadian elements (such as optimal timing for meals and daily oscillation of lipid metabolism activities) might enhance efficacy, ensure safety, or mitigate potential side effects of a drug.…”

Section: Conclusion Significances and Future Directionsmentioning

confidence: 99%

Time‐restricted feeding regulates lipid metabolism under metabolic challenges

Guo,

Livelo,

Melkani

2023

BioEssays

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Dysregulation of lipid metabolism is a commonly observed feature associated with metabolic syndrome and leads to the development of negative health outcomes such as obesity, diabetes mellitus, non‐alcoholic fatty liver disease, or atherosclerosis. Time‐restricted feeding/eating (TRF/TRE), an emerging dietary intervention, has been shown to promote pleiotropic health benefits including the alteration of diurnal expression of genes associated with lipid metabolism, as well as levels of lipid species. Although TRF likely induces a response in multiple organs leading to the modulation of lipid metabolism, a majority of the studies related to TRF effects on lipids have focused only on individual tissues, and furthermore there is a lack of insight into potential underlying mechanisms. In this review, we summarize the current insights regarding TRF effects on lipid metabolism and the potential mechanisms in adipose tissue, liver, skeletal muscle, and heart, and conclude by outlining possible avenues for future exploration.

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“…Although aerobic glycolysis is less efficient in producing ATP compared to oxidative phosphorylation, it generates other metabolites that support tumor growth (Ashrafian, 2006). Lipid supply is crucial for the proliferation and survival of various cancer cells (Liang and Dai, 2022), and previous studies have demonstrated that cancer cells predominantly acquire lipids through the de novo fatty acid synthesis pathway (Baron et al, 2004). Activation of this pathway is believed to be necessary for carcinogenesis (Zhou et al, 2007).…”

Section: Alteration Of Lipid Metabolism In Cancer Cellsmentioning

confidence: 99%

Lipid metabolism as a target for cancer drug resistance: progress and prospects

Wang,

et al. 2023

Front. Pharmacol.

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Cancer is the world’s leading cause of human death today, and the treatment process of cancer is highly complex. Chemotherapy and targeted therapy are commonly used in cancer treatment, and the emergence of drug resistance is a significant problem in cancer treatment. Therefore, the mechanism of drug resistance during cancer treatment has become a hot issue in current research. A series of studies have found that lipid metabolism is closely related to cancer drug resistance. This paper details the changes of lipid metabolism in drug resistance and how lipid metabolism affects drug resistance. More importantly, most studies have reported that combination therapy may lead to changes in lipid-related metabolic pathways, which may reverse the development of cancer drug resistance and enhance or rescue the sensitivity to therapeutic drugs. This paper summarizes the progress of drug design targeting lipid metabolism in improving drug resistance, and providing new ideas and strategies for future tumor treatment. Therefore, this paper reviews the issues of combining medications with lipid metabolism and drug resistance.

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Progress of potential drugs targeted in lipid metabolism research

Cited by 14 publications

References 204 publications

ATP-Citrate Lyase (ACLY): An Extensive Investigation from Molecular Insight to Therapeutic implications

ATP-Citrate Lyase (ACLY): An Extensive Investigation from Molecular Insight to Therapeutic implications

Time‐restricted feeding regulates lipid metabolism under metabolic challenges

Lipid metabolism as a target for cancer drug resistance: progress and prospects

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