Therapeutic potential of the sphingosine kinase 1 inhibitor, PF-543

Yi, Xueliang; Tang, Xuemei; Li, Tianlong; Lin, Ching‐Long; He, Haibo; Wu, Xiaoxiao; Xiang, Chunlin; Cao, Min; Wang, Zixiang; Wang, Yi; Wang, Yiping; Huang, Xiaobo

doi:10.1016/j.biopha.2023.114401

Cited by 10 publications

(2 citation statements)

References 92 publications

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“…Józefczuk et al ( 182 ) have shown that PF543, a selective SphK1 inhibitor, improved the endothelial function of arteries of hypertensive mice. In another study, Wu et al ( 200 ) showed that rats treated with an injection of two different concentrations of PF543 after myocardial infarction, had a reduced expression of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. The higher concentration had a better inhibitory effect, and PF543 improved the cardiac function of rats.…”

Section: Sphingolipids-based Drugs As a Potential Therapy For Cardiov...mentioning

confidence: 99%

The therapeutic potential of sphingolipids for cardiovascular diseases

Ya'ar Bar,

Pintel,

Abd Alghne

et al. 2023

Front. Cardiovasc. Med.

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Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide and Inflammation plays a critical role in the development of CVD. Despite considerable progress in understanding the underlying mechanisms and various treatment options available, significant gaps in therapy necessitate the identification of novel therapeutic targets. Sphingolipids are a family of lipids that have gained attention in recent years as important players in CVDs and the inflammatory processes that underlie their development. As preclinical studies have shown that targeting sphingolipids can modulate inflammation and ameliorate CVDs, targeting sphingolipids has emerged as a promising therapeutic strategy. This review discusses the current understanding of sphingolipids’ involvement in inflammation and cardiovascular diseases, the existing therapeutic approaches and gaps in therapy, and explores the potential of sphingolipids-based drugs as a future avenue for CVD treatment.

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Section: Sphingolipids-based Drugs As a Potential Therapy For Cardiov...mentioning

confidence: 99%

The therapeutic potential of sphingolipids for cardiovascular diseases

Ya'ar Bar,

Pintel,

Abd Alghne

et al. 2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

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“…It has also demonstrated potential in reducing inflammation and autoimmune responses. These collective observations suggest that PF-543, through the inhibition of SphK1 and subsequent modulation of S1P levels, may offer therapeutic promise in the treatment of malignancies and the management of immune-related disorders, presenting a compelling proposition for further exploration and translation into clinical applications ( Yi et al, 2023 ). Another important modulator of SphK1 is fingolimod (FTY720, sold under the brand name Gilenya ® ).…”

Section: Sphingolipid Metabolismmentioning

confidence: 99%

Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology

Jamjoum,

Majumder,

Issleny

et al. 2024

Front. Physiol.

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Metabolic pathways are complex and intertwined. Deficiencies in one or more enzymes in a given pathway are directly linked with genetic diseases, most of them having devastating manifestations. The metabolic pathways undertaken by sphingolipids are diverse and elaborate with ceramide species serving as the hubs of sphingolipid intermediary metabolism and function. Sphingolipids are bioactive lipids that serve a multitude of cellular functions. Being pleiotropic in function, deficiency or overproduction of certain sphingolipids is associated with many genetic and chronic diseases. In this up-to-date review article, we strive to gather recent scientific evidence about sphingolipid metabolism, its enzymes, and regulation. We shed light on the importance of sphingolipid metabolism in a variety of genetic diseases and in nervous and immune system ailments. This is a comprehensive review of the state of the field of sphingolipid biochemistry.

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Brain region specific regulation of anandamide (down) and sphingosine-1-phosphate (up) in association with anxiety (AEA) and resilience (S1P) in a mouse model of chronic unpredictable mild stress

Fischer,

Thomas,

Gurke

et al. 2024

Pflugers Arch - Eur J Physiol

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Chronic unpredictable and unavoidable stress is associated with mental health problems such as depression and anxiety, whereas cycles of stress and stress relief strengthen resilience. It has been suggested that increased breakdown of brain endocannabinoids (eCB) promotes a feeling of adversity. To assess the impact of stress on bioactive lipid homeostasis, we analyzed eCB, sphingolipids, and ceramides in seven brain regions and plasma in a mouse model of chronic unpredictable mild stress. Chronic unpredictable mild stress (CUMS) was associated with low levels of anandamide in hippocampus and prefrontal cortex in association with indicators of anxiety (elevated plus maze). Oppositely, CUMS caused elevated levels of sphingosine-1-phosphate (S1P d18:1) and sphinganine-1-phosphate (S1P d18:0) in the midbrain and thalamus, which was associated with readouts of increased stress resilience, i.e., marble burying and struggling in the tail suspension tests. In the periphery, elevated plasma levels of ceramides revealed similarities with human major depression and suggested unfavorable effects of stress on metabolism, but plasma lipids were not associated with body weight, sucrose consumption, or behavioral features of depression or anxiety. The observed brain site-specific lipid changes suggest that the forebrain succumbs to adverse stress effects while the midbrain takes up defensive adjustments.

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Therapeutic potential of the sphingosine kinase 1 inhibitor, PF-543

Cited by 10 publications

References 92 publications

The therapeutic potential of sphingolipids for cardiovascular diseases

The therapeutic potential of sphingolipids for cardiovascular diseases

Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology

Brain region specific regulation of anandamide (down) and sphingosine-1-phosphate (up) in association with anxiety (AEA) and resilience (S1P) in a mouse model of chronic unpredictable mild stress

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