RP101075

RP101075, an active metabolite of Ozanimod, is a potent, orally active S1PR (sphingosine-1-phosphate receptor 1) agonist, with an EC50 of 0.27 nM. RP101075 displays >100-fold selectivity over S1PR5 (EC50=5.9 nM) and >10000-fold over S1PR 2, 3, and 4. RP101075 displays superior cardiovascular safety profile[1].

Signaling Pathways >> GPCR/G Protein >> LPL Receptor

Research Areas >> Inflammation/Immunology

S1PR1:0.27 nM (EC50)

S1PR5:5.9 nM (EC50)

RP101075 (0.3-0.6 mg/kg; p.o.) significantly attenuated neurological deficits and reduced brain edema in intracerebral hemorrhage (ICH) mice. RP101075 reduced the counts of brain-infiltrating lymphocytes, neutrophils, and microglia, as well as cytokine expression after ICH. Enhanced blood-brain barrier integrity and alleviated neuronal death were also seen in ICH mice after RP101075 treatment[1]. RP101075 (0.3-3 mg/kg; p.o.; daily from week 23 until week 42) inhibits lymphocytes and pDC in the spleens of mice[2]. Animal Model: NZBWF1 female mice[2] Dosage: 0.3, 1, 3 mg/kg Administration: P.o.; daily from week 23 until week 42 Result: Dose-dependent reduction in lymphocytes in the spleen following 20 weeks of treatment; a reduction in plasmacytoid dendritic cells (pDC).

[1]. Sun N, et al. Selective Sphingosine-1-Phosphate Receptor 1 Modulation Attenuates Experimental Intracerebral Hemorrhage. Stroke. 2016;47(7):1899-1906.

[2]. Taylor Meadows KR, et al. Ozanimod (RPC1063), a selective S1PR1 and S1PR5 modulator, reduces chronic inflammation and alleviates kidney pathology in murine systemic lupus erythematosus. PLoS One. 2018;13(4):e0193236. Published 2018 Apr 2.