This is a single-institution, open-labeled study using fingolimod (FTY720/Gilenya) in patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) who have progressed on chemo-immunotherapy. The study design will be a 6 patient safety lead-in with 2 cohorts of patients for efficacy analysis where fingolimod 0.5 mg will be taken orally once daily.

Start Date30 Sep 2024

Sponsor / Collaborator

Medical University of South Carolina

IRCT20240701062291N1 / RecruitingPhase 2IIT

The efficacy of fingolimod in enhancing neurological recovery after traumatic spinal cord injury

Start Date22 Aug 2024

Sponsor / Collaborator

Mashhad University of Medical Sciences

IRCT20200105046010N92 / Recruiting

Bioequivalence study of Fingolimod 0.5 mg capsule manufactured by Abidi Co (Norabex) versus originator brand Gilenya capsule manufactured by Novartis Co in fasting condition in healthy volunteers

Start Date30 Jan 2024

Sponsor / Collaborator-

100 Clinical Results associated with S1PR4 x S1PR3 x S1PR1 x S1PR5

100 Translational Medicine associated with S1PR4 x S1PR3 x S1PR1 x S1PR5

0 Patents (Medical) associated with S1PR4 x S1PR3 x S1PR1 x S1PR5

Literatures (Medical) associated with S1PR4 x S1PR3 x S1PR1 x S1PR5

01 Feb 2024·Drugs

Etrasimod: First Approval

Review

Author: Shirley, Matt

Etrasimod (VELSIPITY™) is an orally available, small-molecule selective sphingosine-1-phosphate (S1P) receptor modulator being developed by Pfizer for the treatment of ulcerative colitis and other immune-mediated inflammatory disorders. Etrasimod is selective for S1P receptor subtypes S1P₁, S1P₄ and S1P₅ while having minimal activity on S1P₃ and no activity on S1P₂. Etrasimod received its first approval, in the USA, in October 2023 for the treatment of moderately to severely active ulcerative colitis in adults. Subsequently, the European Medicines Agency adopted a positive opinion in December 2023, recommending the granting of marketing authorisation for etrasimod for the treatment of patients aged ≥ 16 years with moderately to severely active ulcerative colitis who have had an inadequate response, lost response, or were intolerant to either conventional therapy, or a biological agent. Etrasimod is also under regulatory review for the treatment of ulcerative colitis in several other countries. Clinical development of etrasimod for use in the treatment of Crohn's disease, atopic dermatitis, eosinophilic oesophagitis and alopecia areata is ongoing worldwide. This article summarises the milestones in the development of etrasimod leading to this first approval for the treatment of ulcerative colitis in adults.

01 Jan 2023·Multiple Sclerosis and Related Disorders

The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination

Review

Author: James, Louisa K ; Giovannoni, Gavin ; Pryce, Gareth ; Baker, David ; Schmierer, Klaus ; Forte, Eugenia ; Kang, Angray S

BACKGROUNDSphingosine-one phosphate receptor (S1PR) modulation inhibits S1PR1-mediated lymphocyte migration, lesion formation and positively-impacts on active multiple sclerosis (MS). These S1PR modulatory drugs have different: European Union use restrictions, pharmacokinetics, metabolic profiles and S1PR receptor affinities that may impact MS-management. Importantly, these confer useful properties in dealing with COVID-19, anti-viral drug responses and generating SARS-CoV-2 vaccine responses.OBJECTIVETo examine the biology and emerging data that potentially underpins immunity to the SARS-CoV-2 virus following natural infection and vaccination and determine how this impinges on the use of current sphingosine-one-phosphate modulators used in the treatment of MS.METHODSA literature review was performed, and data on infection, vaccination responses; S1PR distribution and functional activity was extracted from regulatory and academic information within the public domain.OBSERVATIONSMost COVID-19 related information relates to the use of fingolimod. This indicates that continuous S1PR1, S1PR3, S1PR4 and S1PR5 modulation is not associated with a worse prognosis following SARS-CoV-2 infection. Whilst fingolimod use is associated with blunted seroconversion and reduced peripheral T-cell vaccine responses, it appears that people on siponimod, ozanimod and ponesimod exhibit stronger vaccine-responses, which could be related notably to a limited impact on S1PR4 activity. Whilst it is thought that S1PR3 controls B cell function in addition to actions by S1PR1 and S1PR2, this may be species-related effect in rodents that is not yet substantiated in humans, as seen with bradycardia issues. Blunted antibody responses can be related to actions on B and T-cell subsets, germinal centre function and innate-immune biology. Although S1P1R-related functions are seeming central to control of MS and the generation of a fully functional vaccination response; the relative lack of influence on S1PR4-mediated actions on dendritic cells may increase the rate of vaccine-induced seroconversion with the newer generation of S1PR modulators and improve the risk-benefit balance IMPLICATIONS: Although fingolimod is a useful asset in controlling MS, recently-approved S1PR modulators may have beneficial biology related to pharmacokinetics, metabolism and more-restricted targeting that make it easier to generate infection-control and effective anti-viral responses to SARS-COV-2 and other pathogens. Further studies are warranted.

01 Sep 2022·Biomedicine & Pharmacotherapy

Sphingosine 1-phosphate receptor, a new therapeutic direction in different diseases

Review

Author: Tian, Shuxia ; Wu, Tao ; Wang, Junmin ; Chen, Junming ; Zhang, Caiyun ; Ji, Guang ; Ding, Peilun ; Chen, Hongyu

Sphingosine 1-phosphate receptor (S1PR), as a kind of G protein-coupled receptor, has five subtypes, including S1PR1, S1PR2, S1PR3, S1PR4, and S1PR5. Sphingosine 1-phosphate receptor (S1P) and S1PR regulate the trafficking of neutrophils and some cells, which has great effects on immune systems, lung tissue, and liver tissue. Presently, many related reports have proved that S1PR has a strong effect on the migration of lymphocytes, tumor cells, neutrophils, and many other cells via the regulation of signals, pathways, and enzymes. In this way, S1PR can regulate the relative response of the organism. Thus, S1PR has become a possible target for the treatment of autoimmune diseases, pulmonary disease, liver disease, and cancer. In this review, we mainly focus on the research of the S1PR for the new therapeutic directions of different diseases and is expected to assist support in the clinic and drug use.

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