Symmetric molecules with 1,4-triazole moieties as potent inhibitors of tumour-associated lactate dehydrogenase-A

Altamimi, Abdul Malek S.; Alafeefy, Ahmed M.; Balode, Agnese; Vozny, I. V.; Pustenko, Aleksandrs; Shikh, Mohey Eldin El; Alasmary, Fatmah Ali; Abdel-Gawad, Sherif A.; Žalubovskis, Raivis

doi:10.1080/14756366.2017.1404593

Cited by 12 publications

(7 citation statements)

References 26 publications

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“…Recently, molecules with 1,4-triazole moieties have been reported as potent inhibitors of LDH, but they have not been tested for anticancer activity [126].…”

Section: Possible Targets Of Lactate Metabolism and Their Potentiamentioning

confidence: 99%

Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities

Feichtinger

Lang

2019

Journal of Oncology

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Although immunotherapy plays a significant role in tumor therapy, its efficacy is impaired by an immunosuppressive tumor microenvironment. A molecule that contributes to the protumor microenvironment is the metabolic product lactate. Lactate is produced in large amounts by cancer cells in response to either hypoxia or pseudohypoxia, and its presence in excess alters the normal functioning of immune cells. A key enzyme involved in lactate metabolism is lactate dehydrogenase (LDH). Elevated baseline LDH serum levels are associated with poor outcomes of current anticancer (immune) therapies, especially in patients with melanoma. Therefore, targeting LDH and other molecules involved in lactate metabolism might improve the efficacy of immune therapies. This review summarizes current knowledge about lactate metabolism and its role in the tumor microenvironment. Based on that information, we develop a rationale for deploying drugs that target lactate metabolism in combination with immune checkpoint inhibitors to overcome lactate-mediated immune escape of tumor cells.

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“…Recently, molecules with 1,4-triazole moieties have been reported as potent inhibitors of LDH, but they have not been tested for anticancer activity [126].…”

Section: Possible Targets Of Lactate Metabolism and Their Potentiamentioning

confidence: 99%

Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities

Feichtinger

Lang

2019

Journal of Oncology

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“…It generates adequate extracellular lactate to provide a favourable microenvironment for CSCs growth and invasion[75]. Although inhibition of LDHA activity has been proposed as an approach to cancer therapy[76], a limited number of LDHA inhibitors are reported in the literature[77]. However, LDHA is transcriptionally regulated by the oncogenic transcription factor FoxM1[78], and some FoxM1 inhibitors (such as thiostrepton, troglitazone, and the FDI-6 molecule) have been reported that could indirectly lead to a reduction of LDHA[79].…”

Section: Potential Therapies Targeting Pcscsmentioning

confidence: 99%

Pancreatic cancer stem cells: Perspectives on potential therapeutic approaches of pancreatic ductal adenocarcinoma

Carlo¹,

Brandi²,

Cecconi³

2018

WJSC

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Pancreatic ductal adenocarcinoma is one of the most aggressive solid tumours of the pancreas, characterised by a five-year survival rate less than 8%. Recent reports that pancreatic cancer stem cells (PCSCs) contribute to the tumorigenesis, progression, and chemoresistance of pancreatic cancer have prompted the investigation of new therapeutic approaches able to directly target PCSCs. In the present paper the non-cancer related drugs that have been proposed to target CSCs that could potentially combat pancreatic cancer are reviewed and evaluated. The role of some pathways and deregulated proteins in PCSCs as new therapeutic targets are also discussed with a focus on selected specific inhibitors. Finally, advances in the development of nanoparticles for targeting PCSCs and site-specific drug delivery are highlighted, and their limitations considered.

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“…The therapeutic interest for LDH inhibition prompted the development of potent, dual or selective, active-site LDH inhibitors. [24][25][26][27][28][29][30] However, despite intense efforts, pharmacological LDH inhibition struggled to translate to in vivo activity. 27,29,31,32 In fact, LDHs are usually recognized as poorly druggable targets, and different reasons can account for this.…”

Section: Introductionmentioning

confidence: 99%

Discovery of a novel lactate dehydrogenase tetramerization domain using epitope mapping and peptides

Thabault

Liberelle

Koruza

et al. 2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Symmetric molecules with 1,4-triazole moieties as potent inhibitors of tumour-associated lactate dehydrogenase-A

Cited by 12 publications

References 26 publications

Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities

Targeting L-Lactate Metabolism to Overcome Resistance to Immune Therapy of Melanoma and Other Tumor Entities

Pancreatic cancer stem cells: Perspectives on potential therapeutic approaches of pancreatic ductal adenocarcinoma

Discovery of a novel lactate dehydrogenase tetramerization domain using epitope mapping and peptides

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