EDG8 Blocking Peptide
- Known as:
- EDG8 Blocking Peptide
- Catalog number:
- 33r-5958
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Fitzgerald industries international
- Gene target:
- EDG8 Blocking Peptide
Related genes to: EDG8 Blocking Peptide
- Gene:
- S1PR5 NIH gene
- Name:
- sphingosine-1-phosphate receptor 5
- Previous symbol:
- EDG8
- Synonyms:
- Edg-8
- Chromosome:
- 19p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-01-02
- Date modifiied:
- 2014-11-19
Related products to: EDG8 Blocking Peptide
Related articles to: EDG8 Blocking Peptide
- Sphingosine-1-phosphate (S1P) and its five G protein-coupled receptors (S1PR1-S1PR5) regulate a broad range of processes that shape cancer progression, including proliferation, survival, angiogenesis, immune evasion and metastatic dissemination. Under physiological conditions, this signaling axis contributes to vascular integrity, immune cell trafficking and tissue homeostasis. In cancer, however, its output is not solely determined by ligand abundances. Rather, tumors reprogram the S1P-S1PR axis at a number of levels, coupling altered S1P production with receptor-specific changes in expression, localization and the signaling state to generate context-dependent malignant phenotypes. The present review provided a receptor-resolved synthesis of S1PR functions in cancer and examined the mechanisms that underlie pathway dysregulation, including transcriptional activation, epigenetic remodeling, microRNA loss, post-translational modifications and altered receptor trafficking and compartmentalization. It further discussed how metabolic amplification of S1P availability cooperates with receptor-level rewiring to sustain tumor progression, microenvironmental remodeling and therapeutic resistance. This framework positions the S1P-S1PR axis as a dynamically reprogrammed signaling network and highlights therapeutic strategies that concurrently target S1P production and receptor-mediated signaling as promising avenues for more-precise, biomarker-informed cancer treatment. - Source: PubMed
Publication date: 2026/05/04
Chuang Yun-TaWu I-HuiLee Cheng-FanLee Hsinyu - Sphingosine-1-phosphate (S1P) is a crucial sphingolipid mediator in vasculature and neovascular eye diseases by controlling angiogenesis, inflammation and fibrosis. Five S1P receptors (S1PRs) are key therapeutic targets, with several S1PR-targeted drugs already in clinical use or trials. However, the vascular function of its major metabolic product, the reactive lipid aldehyde 2-hexadecenal (2-HD), remains unexplored. Here, we show that loss of the aldehyde dehydrogenase ALDH3B1 impairs 2-HD detoxification and leads to retinal vascular abnormalities in zebrafish, without affecting the trunk vasculature. Mechanistically, multi-omics analyses reveal that 2-HD accumulation disrupts iron homeostasis and induces ferroptosis by directly interacting with S1PR5. This finding is supported by integrative analyses of single-cell RNA sequencing and RNA sequencing from human neovascular retinal samples, identifying S1PR5 as a clinically relevant target. These findings uncover a previously unrecognized role of S1P derived 2-HD in vasculature and retinal vascular homeostasis, suggesting that targeting S1PR5 could offer a therapeutic strategy for diabetic retinopathy. - Source: PubMed
Publication date: 2026/04/14
Qian XinGe RuiChu YintengKuang TianZhang XinBennewitz KatrinLou BowenHao WeijieAst VolkerKlinke GlynisPoschet GernotMorgenstern JakobFleming ThomasHausser IngridSzendroedi JuliaNawroth Peter PaulKroll Jens - Sphingosine-1-phosphate (S1P), a key metabolite of sphingolipids, plays crucial roles in a wide range of physiological and pathological processes. S1P primarily exerts its functions by binding to G protein-coupled sphingosine-1-phosphate receptors (S1PRs), which comprise five subtypes (S1PR1-5) in humans, thereby activating these receptors and their downstream signaling pathways. Understanding the molecular determinants that govern agonist selectivity among different S1PR subtypes is vital for the rational and precise development of targeted therapeutic agents. Here, four cryo-electron microscopy structures of agonist-bound S1PR1-Gi1 complexes are reported. Through an integrated approach combining structural analysis, molecular dynamics simulations, and pharmacological assays, the molecular basis for the selectivity of CYM5442, HY-X-1011, Ponesimod, and SAR247799 toward S1PR1 over S1PR2-S1PR5 is uncovered. Nonconserved residues within the ligand-binding pocket and at the Gi1-protein interface contribute to S1PR1 selectivity by these agonists. A distinct agonist binding orientation toward transmembrane helices 5-7, combined with branched substituents that increase the agonist's molecular width, results in steric clashes with residues in S1PR3. Additionally, branched moieties located at the tail portions of the agonist restrict its deep insertion into the binding pocket of both S1PR3 and S1PR5. These structural features collectively enhance its selectivity for S1PR1 over S1PR3 and S1PR5. Furthermore, polar interactions with conserved polar residues in the top region of the binding pocket also influence agonist selectivity. Besides, the relatively broad molecular width of the agonist sterically hinders its binding into S1PR2 and S1PR4 pocket by nonconserved residue pairs bearing bulky side chains. These findings establish a structural framework for the rational design of next-generation S1PR1 highly selective agonists with improved therapeutic potential. - Source: PubMed
Publication date: 2026/04/10
Yu LeiyeJiao HaizhanPang BinTi RujuanGan BingQin ZhaoyangWang JinxinZhu LizheHu HongliRen Ruobing - Atopic dermatitis (AD) is a common inflammatory skin disease associated with Th2, Th9, and Th22 skewing. Recent studies have implicated various lipid mediators in modulating T helper cell responses. However, the relationship between lipid mediators and Th skewing in AD is not fully understood. - Source: PubMed
Publication date: 2026/03/17
Yamamura KazuhikoGarcet SandraGonzalez JuanaZhou JerryFiedler JacobMiura ShunsukeWilliams Samuel CHur Hong BeomMurai-Yamamura MikaLi XuanRenert-Yuval YaelEstrada YerielKrueger James GGuttman-Yassky Emma - Tissue-resident lymphocytes can recirculate, but the underlying molecular mechanism is poorly understood. During helminth infection, intestinal group 2 innate lymphoid cells (ILC2s) rapidly proliferate and give rise to inflammatory ILC2s (iILC2s), which migrate from the intestine to distal tissues. Here, we show in mice that the redistribution of iILC2s requires access to lymphatic vessels. Interleukin-25 (IL-25) induces a substantial change in the epigenetic landscape of iILC2s, with transcription factors KLF2 and ZEB2 driving increased expression of sphingosine-1-phosphate receptor 1 (S1PR1) and S1PR5, respectively. S1PR5 regulates iILC2 exit from the intestine to the lymph, whereas S1PR1 is critical for iILC2 egress from the mesenteric lymph nodes to the blood and then to distal tissues including the lung, where iILC2s contribute to tissue repair. The requirement of two S1PRs is largely due to the dynamic expression of CD69, which mediates S1PR1 internalization. Thus, S1PRs modulate iILC2 emigration from nonlymphoid and lymphoid organs in a stage-specific manner, which provides a framework for understanding the multistep migration of tissue-resident immune cells. - Source: PubMed
Publication date: 2026/03/13
Ito TakamasaWu Christine FZhang YingyuIshida YoshihiroGretarsson Kristjan HXu XinjingZou RaymondGuichard VincentHuang Lei HHan Richard PGuckian KevinChun JeroldQue JianwenSmith AllenUrban Joseph FLu ChaoHuang Yuefeng