BAF312 (Siponimod) is a next-generation S1P receptor agonist, selective for S1P1 and S1P5 receptors with EC50 of 0.39 nM and 0.98 nM, exhibits >1000-fold selectivity over S1P2, S1P3 and S1P4 receptors. Phase 3.
Storage Temp
Store at -20°C,Argon charged
Shipped In
Ice chest + Ice pads
Grade
Moligand™
Action Type
AGONIST
Mechanism of action
Sphingosine 1-phosphate receptor Edg-1 agonist
Product Description
Information
Siponimod (BAF312) BAF312 (Siponimod) is a next-generation S1P receptor agonist, selective for S1P1 and S1P5 receptors with EC50 of 0.39 nM and 0.98 nM, exhibits >1000-fold selectivity over S1P2, S1P3 and S1P4 receptors. Phase 3.
BAF312 (Siponimod) is a potent and selective S1P receptor agonist, with EC50 of 0.39 nM and 0.98 nM for S1P1 and S1P5receptors, exhibits >1000-fold selectivity over S1P2, S1P3 and S1P4 receptors. BAF312 (1 h at 1 μM) promotes prominent internalization of S1P1 receptors by 91%.
In vivo
BAF312 effectively suppresses encephalomyelitis (EAE) in rats by internalizing S1P1 receptors, rendering them insensitive to the egress signal from lymph nodes. BAF312 significantly reduces clinical scores when dosed prophylactically or therapeutically in mice at 0.3 mg/kg.
1.Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG et al.. (2012) The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate.. Br J Pharmacol, 167 (5):(1035-47). [PMID:22646698]
2.Lewis ND, Haxhinasto SA, Anderson SM, Stefanopoulos DE, Fogal SE, Adusumalli P, Desai SN, Patnaude LA, Lukas SM, Ryan KR et al.. (2013) Circulating monocytes are reduced by sphingosine-1-phosphate receptor modulators independently of S1P3.. J Immunol, 190 (7):(3533-40). [PMID:23436932]
3.O'Sullivan C, Schubart A, Mir AK, Dev KK. (2016) The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures.. J Neuroinflammation, 13 (3):(31). [PMID:26856814]
4.Pan S, Gray NS, Gao W, Mi Y, Fan Y, Wang X, Tuntland T, Che J, Lefebvre S, Chen Y et al.. (2013) Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator.. ACS Med Chem Lett, 4 (3):(333-7). [PMID:24900670]
G2228168