S1PR1 (Sphingosine-1-Phosphate Receptor 1)

Molecular docking and dynamics simulations showed that R120P and F125S weaken binding affinity for natural agonist sphingosine-1-phosphate (S1P) and FTY720P, while antagonist W146 retained strong binding...Collectively, these findings identified high-risk nsSNPs in S1PR1 gene with potential structural and functional implications, particularly in diseases involving impaired receptor signaling. These findings enhanced our understanding of how specific nsSNPs can influence disease susceptibility, drug response, and receptor function, paving the way for precision medicine approaches in treating autoimmune and inflammatory disorders.

Furthermore, repurposing paroxetine, one of the Food and Drug Administration-approved selective serotonin reuptake inhibitors (SSRIs) with GRK-2 inhibitory action, enhanced this effect, leading to greater lymphocyte circulation, activation, and improved survival in an orthotopic syngeneic mouse model. By overcoming key mechanisms of immune suppression and repurposing a widely available, clinically safe drug, this strategy represents a highly translatable approach to enhancing the efficacy of immunovirotherapy for gliomas.

Importantly, inhibition of the S1P/S1PR1 signaling pathway down-regulates the expression of S100A8/A9 and suppresses the growth of HPV-KI cells and xenograft derived from cervical cancer patient. These findings provide novel insights into HPV integration-induced cervical carcinogenesis and identify potential therapeutic targets for its treatment.

The results indicate that JGTCs can significantly alleviate inflammatory injury in the prostate tissue of EAP rats. Its mechanism may involve regulating intestinal microbiota dysbiosis and metabolic disorders and inhibiting the activation of the SPHK1/S1P1/PI3K/Akt signaling pathway.

Shengmai San effectively attenuates irradiation-induced salivary gland hypofunction and fibrosis, mainly through inhibition of the SPHK1-S1P-S1PR1 signaling pathway.

Here, we develop a multifunctional nanoplatform in which irradiated tumor lysate-pulsed dendritic cell (DC) membranes wrap lipid nanoparticles, enabling the codelivery of the β-adrenergic receptor blocker carvedilol and S1PR1 mRNA...In combination with PD-L1 blockade, this approach reinforced effector function in tumors, reduced tumor volume by 76%, extended median survival from 30 to 54 days, and achieved complete regression in 60% of animals. By simultaneously targeting priming, trafficking, activation, and exhaustion, this strategy provides an integrated approach to overcoming resistance in breast cancer.

Knockdown of arginine-specific single ADP ribosyltransferase 1 (ART1) can delay the growth of CRC and promote the inhibitory effect of OXA on CRC cell proliferation. Consequently, in a high-CHO environment, this study aims to investigate the impact of ART1 knockdown in CRC cells treated with OXA and on the growth of transplanted tumours in mice in vivo.

Overall, our results indicated that S1PR1 expression at the protein level has a positive relationship with thyroid cancer progression, as seen in other cancers. These data also suggest that quercetin is a potential anticancer drug that can target S1PR1-positive cells.

This study identifies CHEMBL1540377 as a potent analogue targeting S1PR1 for NHL therapy. The combination of computational and experimental findings provides a strong foundation for future research and potential clinical application of S1P analogues in treating NHL.

Mice with EC-specifically MYPT1-deficient (Mypt1ΔEC) also showed coronary endothelial hyperpermeability, and treatment with the S1PR1 agonist FTY720 failed in alleviating the pathological effects. At 1 month post-transverse aortic constriction, both Mypt1ΔEC and S1pr1ΔEC mice displayed aggravated pathological cardiac remodeling. These findings suggest that the S1PR1-MYPT1 signaling is crucial for coronary endothelial permeability and myocardial microenvironmental homeostasis under pressure overload, targeting which may offer therapeutic potential for related heart diseases.

Our research indicates that FTY720 may inhibit NSCLC via possible targets ZEB2 and S1PR1, further laying the theoretical foundation for the utilization of FTY720 in NSCLC treatment.

S1P1 contributes to the immunosuppressive phenotype of microglia. Inhibiting the S1P/S1P1 axis impairs viability and crosstalk between melanoma cells and tumor-activated microglia, offering a potential therapeutic strategy for melanoma brain metastases.