It is an oral and selective sphingosine 1-phosphate 1 (S1PR1) and 5 (S1PR5
) receptor modulator in development for immune-inflammatory indications such as ulcerative colitis and Crohn's disease, in addition to multiple sclerosis.
For the evaluation of S1PR4 and S1PR5 mRNA expression, double amount of cDNA (4 [micro]l) was used and 40 cycles of amplification performed.
First, we analysed by reverse transcription and real-time PCR the expression of the five S1P receptor (S1PR) subtypes and we found that BM-MSCs expressed three of five S1PRs, S1PR1, S1PR2, and S1PR3 (Figures 1(a) and 1(b)), whereas in this experimental conditions, S1PR4 and S1PR5 subtypes were not detectable.
mRNA were determined by RT of total RNA (1 [micro]g) obtained from BM-MSCs at low--(L-) and high--(H-) density culture and 2 [micro]l of cDNA (for S1PR1, S1PR2, and S1PR3 detection) or 4 [micro]l of cDNA (for S1PR4 and S1PR5 detection) were amplified as described in Section 2.
In immature neurons, the activation of S1PR1 activates neurite outgrowth whereas S1PR2 or S1PR5
exerts inhibitory effects in vitro .
FTY720-phosphate functions as a noncompetitive inhibitor of various S1PRs [30,31], such as S1PR1, S1PR3, S1PR4, and S1PR5
, but not S1PR2, receptors [27, 32, 33].
(NASDAQ: CELG) has released detailed results from the phase III SUNBEAM trial evaluating the efficacy and safety of ozanimod, a novel, oral, selective sphingosine 1-phosphate 1 (S1PR1) and 5 (S1PR5
) receptor modulator, versus a first-line treatment, Avonex (interferon beta-1a; IFN), in patients with relapsing multiple sclerosis (RMS), the company said.
S1PR4 is exclusively found in hematopoietic tissues under basal conditions , whereas S1PR5 expression is restricted to natural killer (NK) cells , dendritic cells (DCs) , the central nervous system , endothelial cells , and certain cancer cells [28, 29], indicating specialized functions of these two S1PRs.
B cells utilize S1PR1 and 3 to localize to their proper locations in secondary lymphoid organs [5, 35], and NK cell migration towards S1P depends on S1PR5 .
Ozanimod is a novel, oral, selective, sphingosine 1-phosphate 1 (S1PR1) and 5 (S1PR5
) receptor modulator in development for immune-inflammatory indications including relapsing multiple sclerosis, ulcerative colitis, and Crohn's disease.
Selective binding with S1PR5
receptors is believed to activate specific cells within the CNS.
S1PR1 is expressed in most immune cells, whereas S1PR5
is expressed primarily by DCs and NK cells.