Building on our work with the structurally related compound KRP203, we show that high-dose FTY720 produces isozyme-divergent modulation across phosphoinositide kinases and biases PIKFYVE activity toward phosphatidylinositol, a pattern we term ASURA (Asymmetric Simultaneous Uncoupling of Related Activities). Patient-derived glioblastoma (GBM) neurospheres were sensitive to FTY720, and co-treatment with a PI3Kα-selective inhibitor augmented growth suppression in U87MG cells. Together, these data support a model in which ASURA-dose FTY720 disrupts phosphoinositide-regulated trafficking and nutrient access, imposing intracellular nutrient stress that culminates in tumor-cell death.

P1, N=6, Completed, Viatris Innovation GmbH | Active, not recruiting --> Completed

Pharmacological intervention with the sphingosine-1-phosphate receptor modulator siponimod during cuprizone intoxication attenuated OLIG2 protein loss, indicating that this stress-induced state is pharmacologically modifiable...Thus, OLIG2 protein loss may serve as an early indicator of oligodendrocyte stress and a possible therapeutic target for preserving myelin integrity in demyelinating disorders. These findings have additional methodological implications as stressed oligodendrocytes may evade detection using OLIG2-based lineage markers.

P2, N=105, Recruiting, St. Joseph's Hospital and Medical Center, Phoenix | Not yet recruiting --> Recruiting

The combination of Bevacizumab and Fingolimod presents a promising treatment strategy for ovarian cancer.

P3, N=300, Recruiting, Viatris Innovation GmbH | Not yet recruiting --> Recruiting

P1, N=6, Recruiting, Viatris Innovation GmbH

P3, N=451, Active, not recruiting, Viatris Innovation GmbH | Recruiting --> Active, not recruiting

FTY720, an S1P receptor antagonist, significantly inhibits ER stress-induced IEC injury. Our findings highlight the pathogenic role of host SPHK1 in gastrointestinal injury during aGVHD and suggest that targeting SPHK1 could be a therapeutic strategy for managing this condition.

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.

P2, N=15, Enrolling by invitation, Viatris Pharmaceuticals Co., Ltd. | Not yet recruiting --> Enrolling by invitation