Syrosingopine

“…Syrosingopine, for instance, a dual blocker of MCT1 and MCT4, used for treatment of hypertension several decades ago, is well tolerable. Depression, lethargy or fatigue, and nasal congestion with acceptable severity were observed in some patients [27]. Benjamin et al showed that dual inhibition of MCT1 and MCT4 with syrosingopine, thus inhibiting lactate transport, is not cytotoxic itself but only when oxidative phosphorylation is also inhibited (30540938).…”

Section: Discussionmentioning

confidence: 99%

A Holistic Evolutionary and 3D Pharmacophore Modelling Study Provides Insights into the Metabolism, Function, and Substrate Selectivity of the Human Monocarboxylate Transporter 4 (hMCT4)

Papakonstantinou

Vlachakis

Thireou

et al. 2021

IJMS

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Monocarboxylate transporters (MCTs) are of great research interest for their role in cancer cell metabolism and their potential ability to transport pharmacologically relevant compounds across the membrane. Each member of the MCT family could potentially provide novel therapeutic approaches to various diseases. The major differences among MCTs are related to each of their specific metabolic roles, their relative substrate and inhibitor affinities, the regulation of their expression, their intracellular localization, and their tissue distribution. MCT4 is the main mediator for the efflux of L-lactate produced in the cell. Thus, MCT4 maintains the glycolytic phenotype of the cancer cell by supplying the molecular resources for tumor cell proliferation and promotes the acidification of the extracellular microenvironment from the co-transport of protons. A promising therapeutic strategy in anti-cancer drug design is the selective inhibition of MCT4 for the glycolytic suppression of solid tumors. A small number of studies indicate molecules for dual inhibition of MCT1 and MCT4; however, no selective inhibitor with high-affinity for MCT4 has been identified. In this study, we attempt to approach the structural characteristics of MCT4 through an in silico pipeline for molecular modelling and pharmacophore elucidation towards the identification of specific inhibitors as a novel anti-cancer strategy.

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Metabolic regulation in normal and leukemic stem cells

Man,

Li,

et al. 2024

Trends in Pharmacological Sciences

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Syrosingopine

Cited by 6 publications

References 9 publications

Syrosingopine sensitizes cancer cells to killing by metformin

Syrosingopine sensitizes cancer cells to killing by metformin

A Holistic Evolutionary and 3D Pharmacophore Modelling Study Provides Insights into the Metabolism, Function, and Substrate Selectivity of the Human Monocarboxylate Transporter 4 (hMCT4)

Metabolic regulation in normal and leukemic stem cells

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