Evaluation of pyrrolidine-based analog of jaspine B as potential SphK1 inhibitors against rheumatoid arthritis

Chen, Haijiao; Yang, Haoran; Zhi, Yuee; Yao, Qingqiang

doi:10.1016/j.bmcl.2020.127754

Cited by 14 publications

(13 citation statements)

References 19 publications

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“…In recent years, relevant studies have shown that both SphK 1 expression and S1P secretion are increased in the synovium of RA patients (Lin et al, 2014; Pan et al, 2017; Hyab et al, 2020; Yoo et al, 2012; Yu et al, 2004). S1P can promote proliferation, survival, and migration of synovial fibroblasts (Maceyka et al, 2005; Maceyka & Spiegel, 2014; Wallington‐Beddoe et al, 2019), and can increase the production of cytokines and other pro‐inflammatory mediators (Baker et al, 2013; Chen et al, 2020; Pitman et al, 2016; Wang, Min, et al, 2013). Chiao et al, (2013) reported the synthesis of SphK 1 inhibitor 2‐ epi ‐jaspine B analogues.…”

Section: Chemical Drug Therapy For Rheumatoid Arthritismentioning

confidence: 99%

Some important inhibitors and mechanisms of rheumatoid arthritis

Zhou

Huang

2022

Chem Biol Drug Des

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Rheumatoid arthritis (RA) is a chronic disease that seriously affects human health and quality of life, and it is one of the main causes of labor loss and disability.Many countries have listed rheumatoid arthritis as one of the national a key diseases to tackle. The pathogenesis of RA in humans is still unknown, and medical researchers believe that the pathogenesis of RA may be the result of a combination of genetic and environmental factors. RA is an incurable condition that can only be controlled and treated with conventional drugs. In this paper, the pathologic features and pathogenesis of RA were introduced, and the research progress of new anti-rheumatoid arthritis chemical drugs in recent years was reviewed.

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Section: Chemical Drug Therapy For Rheumatoid Arthritismentioning

confidence: 99%

Some important inhibitors and mechanisms of rheumatoid arthritis

Zhou

Huang

2022

Chem Biol Drug Des

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“…Structurally, the replacement of the furan ring by a pyrrole ring in CHJ01 may account for the stronger activity. Pharmacological experiments showed that CHJ01 exhibited anti-inflammatory effects similar to those of methotrexate in vitro and in vivo by reducing the swelling volume, arthritis score, spleen index and IL-1β, TNF-α, IL-6 levels in arthritis model rats, which contributed to the significant improvement of RA symptoms ( Chen et al, 2021a ).…”

Section: Sphingosine Kinase 1 Selective Inhibitorsmentioning

confidence: 99%

“…In addition, it has been proved that more SphK1 inhibitors have been developed based on existing inhibitor structures or obtained from natural products. For example, jasmine B analogues based on pyrrolidine exerting anti-inflammatory activity for the treatment of RA ( Chen et al, 2021a ); therapeutic effect of SKI-349 obtained by optimizing SKI-178 structure on hematological malignancies ( Hengst et al, 2020b ); and the inhibitors derived form natural products with potential roles in the prevention of breast and lung cancer ( Jairajpuri et al, 2020 ; Khan et al, 2020 ; Roy et al, 2020 ). More compounds with inhibitory activity have been developed and researched due to the benefits of SphK1 inhibitors have been proved.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of SphK1 Inhibitors Based on Abnormal Expression of SphK1 in Inflammatory Immune Related-Diseases

Hong

Deng

2021

Front. Pharmacol.

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Sphingosine kinase 1(SphK1) a key enzyme that catalyzes the conversion of sphingosine (Sph) to sphingosine 1-phosphate (S1P), so as to maintain the dynamic balance of sphingolipid-rheostat in cells and participate in cell growth and death, proliferation and migration, vasoconstriction and remodeling, inflammation and metabolism. The normal expression of SphK1 maintains the balance of physiological and pathological states, which is reflected in the regulation of inflammatory factor secretion, immune response in traditional immune cells and non-traditional immune cells, and complex signal transduction. However, abnormal SphK1 expression and activity are found in various inflammatory and immune related-diseases, such as hypertension, atherosclerosis, Alzheimer’s disease, inflammatory bowel disease and rheumatoid arthritis. In view of the therapeutic potential of regulating SphK1 and its signal, the current research is aimed at SphK1 inhibitors, such as SphK1 selective inhibitors and dual SphK1/2 inhibitor, and other compounds with inhibitory potency. This review explores the regulatory role of over-expressed SphK1 in inflammatory and immune related-diseases, and investigate the latest progress of SphK1 inhibitors and the improvement of disease or pathological state.

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“…S1P induces angiogenesis by regulating the pathological processes of different cell types. Excessive proliferation of FLSs and VECs is an important feature in the pathogenesis of RA, leading to synovial hyperplasia and angiogenesis (Chen, Yang, Zhi, Yao, & Liu, 2021).…”

Section: Introductionmentioning

confidence: 99%

The interplay between fibroblast‐like synovial and vascular endothelial cells leads to angiogenesis via the sphingosine‐1‐phosphate‐induced RhoA‐F‐Actin and Ras‐Erk1/2 pathways and the intervention of geniposide

Deng

et al. 2021

Phytotherapy Research

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The changes of fibroblast‐like synoviocytes (FLSs) and vascular endothelial cells (VECs) biological functions are closely related to angiogenesis in rheumatoid arthritis (RA). Nevertheless, how the crosstalk between FLSs and VECs interferes with RA is far from being clarified. Herein, we studied the effect of the reciprocal interactions between FLSs and VECs on angiogenesis and mechanism of geniposide (GE). After administration of GE, improvement of synovial hyperplasia in adjuvant arthritis rats was accompanied by downregulation of SphK1 and p‐Erk1/2. The dynamic interaction between FLSs and VECs triggers the release of S1P by activating p‐Erk1/2 and SphK1, then activating RhoA‐F‐actin and Ras‐Erk1/2 pathways. When exposed to the inflammatory microenvironment mediated by FLSs‐VECs crosstalk, proliferation, migration, and permeability of VECs were enhanced, the angiogenic factors were imbalanced. Meanwhile, the proliferation and secretory ability of FLSs increased. Interestingly, depletion of S1P or blocking of the activation of SphK1 by GE and PF‐543 prevented the changes. In conclusion, S1P released during FLSs‐VECs crosstalk changed their biological functions by activating RhoA‐F‐actin and Ras‐Erk1/2 pathways. GE acted on p‐Erk1/2 and SphK1, inhibited the secretion of S1P, and blocked the interplay between FLSs and VECs. These results provide new insights into the mechanism of angiogenesis in RA.

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Evaluation of pyrrolidine-based analog of jaspine B as potential SphK1 inhibitors against rheumatoid arthritis

Cited by 14 publications

References 19 publications

Some important inhibitors and mechanisms of rheumatoid arthritis

Some important inhibitors and mechanisms of rheumatoid arthritis

Therapeutic Potential of SphK1 Inhibitors Based on Abnormal Expression of SphK1 in Inflammatory Immune Related-Diseases

The interplay between fibroblast‐like synovial and vascular endothelial cells leads to angiogenesis via the sphingosine‐1‐phosphate‐induced RhoA‐F‐Actin and Ras‐Erk1/2 pathways and the intervention of geniposide

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