S1P1 agonist 1

COVID-19-immunoregulation

Room Temperature

443.88

Inflammation/Immunology

GPCR/G Protein

AKP-11 is a S1P1 agonist with immunomodulatory activities.
In Vitro: AKP-11 binds to S1P1 is internalized and activates intracellular AKT and ERKs cellular signaling pathways. AKP-11 mediated S1P1 downregulation is independent of sphingosine kinase activity indicating it to be a direct agonist of S1P1. AKP-11 decreases cell surface expression of S1P1 in in vitro cell culture model^[1].
In Vivo: AKP-11 (1.3mg/kg) attenuates EAE disease. EAE is the animal model of multiple sclerosis which is extensively used for investigating clinical studies for multiple sclerosis drugs. AKP-11 treatment reduces peripheral total blood lymphocyte and T lymphocyte counts significantly. The reduction in total lymphocytes and T cells are 48% and 41% in AKP-11 treated animals, respectively. The reduction in the CD4+ and CD8+ T cell populations are 41% and 40% in AKP-11 treated animals, respectively. AKP-11 treatment reduces CNS infiltration of T cells and Cytokines and enhances neuroprotection. AKP-11 treatment has little effect on the heart rate of animals. The decrease in blood pressure is also smaller with AKP-11 treatment as compared animals treated with FTY720^[1].