Sphingosine-1-Phosphate Receptor Subtype 1 (S1P1) Modulator IMMH001 Regulates Adjuvant- and Collagen-Induced Arthritis

Jin, Jing; Ji, Ming; Fu, Rong; Wang, Mingjin; Xue, Nina; Xiao, Qiong; Hu, Jingpin; Wang, Xiaojian; Lai, Fangfang; Yin, Daqiang; Chen, Xiaoguang

doi:10.3389/fphar.2019.01085

Cited by 11 publications

(4 citation statements)

References 36 publications

(46 reference statements)

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“…Recently, IMMH001 (SYL930), a S1PR1 and S1PR4 modulator, inhibited arthritis progression in Sprague-Dawley rats, improving hind paw swelling and arthritis index, diminishing pro-inflammatory cytokines and chemokines in damaged joints. Despite these encouraging results, there are no ongoing clinical studies in RA [ 96 ].…”

Section: S1pr Agonists/modulators In Immunological Disordersmentioning

confidence: 99%

Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis

Pérez-Jeldres

Álvarez-Lobos

Rivera–Nieves

2021

Drugs

110

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Sphingosine-1-phosphate (S1P) is a bioactive lipid metabolite that exerts its actions by engaging 5 G-protein-coupled receptors (S1PR1-S1PR5). S1P receptors are involved in several cellular and physiological events, including lymphocyte/hematopoietic cell trafficking. An S1P gradient (low in tissues, high in blood), maintained by synthetic and degradative enzymes, regulates lymphocyte trafficking. Because lymphocytes live long (which is critical for adaptive immunity) and recirculate thousands of times, the S1P-S1PR pathway is involved in the pathogenesis of immune-mediated diseases. The S1PR1 modulators lead to receptor internalization, subsequent ubiquitination, and proteasome degradation, which renders lymphocytes incapable of following the S1P gradient and prevents their access to inflammation sites. These drugs might also block lymphocyte egress from lymph nodes by inhibiting transendothelial migration. Targeting S1PRs as a therapeutic strategy was first employed for multiple sclerosis (MS), and four S1P modulators (fingolimod, siponimod, ozanimod, and ponesimod) are currently approved for its treatment. New S1PR modulators are under clinical development for MS, and their uses are being evaluated to treat other immune-mediated diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis. A clinical trial in patients with COVID-19 treated with ozanimod is ongoing. Ozanimod and etrasimod have shown promising results in IBD; while in phase 2 clinical trials, ponesimod has shown improvement in 77% of the patients with psoriasis. Cenerimod and amiselimod have been tested in SLE patients. Fingolimod, etrasimod, and IMMH001 have shown efficacy in RA preclinical studies. Concerns relating to S1PR modulators are leukopenia, anemia, transaminase elevation, macular edema, teratogenicity, pulmonary disorders, infections, and cardiovascular events. Furthermore, S1PR modulators exhibit different pharmacokinetics; a well-established first-dose event associated with S1PR modulators can be mitigated by gradual up-titration. In conclusion, S1P modulators represent a novel and promising therapeutic strategy for immune-mediated diseases.

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Section: S1pr Agonists/modulators In Immunological Disordersmentioning

confidence: 99%

Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis

Pérez-Jeldres

Álvarez-Lobos

Rivera–Nieves

2021

Drugs

110

View full text Add to dashboard Cite

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“…S1P plays a fundamental role in the immune system. It has been evaluated as a therapeutic target for several immune-mediated disorders beyond UC, such as multiple sclerosis (MS) [64,65], psoriasis [66], rheumatoid arthritis [67], systemic lupus erythematosus [68]. In fact, ozanimod has been authorized for clinically isolated syndrome, relapsing-remitting MS by the EMA and for active secondary progressive MS by the FDA [27].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of S1P1 Receptor Modulator Drugs for Patients with Moderate-to-Severe Ulcerative Colitis

Bencardino,

D’Amico,

Faggiani

et al. 2023

JCM

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Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that negatively impacts patients’ quality of life. In the last decades, the therapeutic options available for the management of patients with moderate to severe UC have increased significantly, including not only biological drugs but also small molecules. However, there is a persistent need to develop new drugs that act on new targets while minimizing the risk of adverse events. Sphingosine-1-phosphate (S1P) is a membrane-derived lysophospholipid. The S1P gradient between tissues and the circulatory system has a key role in regulating the trafficking of immune cells as autoreactive B and T lymphocytes. S1P receptor modulators could be a safe and efficacious alternative mechanism for reducing inflammation in immune-mediated disorders, including UC, by reducing lymphocyte egress from the lymph nodes to the bloodstream. Several S1P receptor modulators have been developed and tested in UC. Ozanimod is already approved by Food and Drug Administration (FDA) and European Medical Agency (EMA), while etrasimod and VTX002 are still under approval. Oral administration route, rapidity and reliable safety profile are the main advantages of this class of drugs. The aim of this review is to summarize the available evidence for the efficacy, safety, and pharmacokinetics of ozanimod, etrasimod, and VTX002 in UC.

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“…Additionally, gardenia glycosides can also suppress the SPHK1/S1P pathway to alleviate vascular endothelial cells stimulation caused by FLS, inhibit angiogenesis, and attain therapeutic effects [ 106 ]. Recently, S001PR930 and the S1PR1 modulator IMMH1 (SYL4) inhibited the progression of arthritis in Sprague-Dawley rats, as evidenced by reduced hind paw swelling and reduced arthritis index, alongside decreased levels of pro-inflammatory cytokines and chemokines in affected joints [ 107 ]. Despite these promising outcomes observed in animal studies, no ongoing clinical studies have been conducted on individuals with RA.…”

Section: Role Of S1p and S1prs In Rheumatoid Arthritismentioning

confidence: 99%

S1P/S1PR signaling pathway advancements in autoimmune diseases

Huang

Zhang

et al. 2023

Biomol Biomed

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Sphingosine-1-phosphate (S1P) is a versatile sphingolipid that is generated through the phosphorylation of sphingosine by sphingosine kinase (SPHK). S1P exerts its functional effects by binding to the G protein-coupled S1P receptor (S1PR). This lipid mediator plays a pivotal role in various cellular activities. The S1P/S1PR signaling pathway is implicated in the pathogenesis of immune-mediated diseases, significantly contributing to the functioning of the immune system. It plays a crucial role in diverse physiological and pathophysiological processes, including cell survival, proliferation, migration, immune cell recruitment, synthesis of inflammatory mediators, and the formation of lymphatic and blood vessels. However, the full extent of the involvement of this signaling pathway in the development of autoimmune diseases remains to be fully elucidated. Therefore, this study aims to comprehensively review recent research on the S1P/S1PR axis in diseases related to autoimmunity.

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Sphingosine-1-Phosphate Receptor Subtype 1 (S1P1) Modulator IMMH001 Regulates Adjuvant- and Collagen-Induced Arthritis

Cited by 11 publications

References 36 publications

Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis

Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis

Efficacy and Safety of S1P1 Receptor Modulator Drugs for Patients with Moderate-to-Severe Ulcerative Colitis

S1P/S1PR signaling pathway advancements in autoimmune diseases

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