NIBR0213

NIBR0213 is an orally bioavailable, potent, and selective antagonist of sphingosine-1-phosphate receptor-1 (S1P1) with IC50 values of 2.5 and 2.0 nM for the hS1P1 in a Ca2+ mobilization assay and GTPgammaS assay, respectively. It is inactive at S1P2, S1P3, and S1P4 receptors (IC50s = >20, >10, and >10 µM, respectively in a Ca2+ mobilization assay). S1P1 plays a key role in the immune system, regulating lymphocyte egress from lymphoid tissues into the circulation. In rats, NIBR0213 (30 mg/kg) reduces peripheral blood lymphocytes by 75-85% for up to 24 hours. In a mouse model of experimental autoimmune encephalitis (EAE), it significantly reduces disease severity up to 26 days, when administered at 30 mg/kg twice per day for three days, then 60 mg/kg twice per day. However, in a rat model of adjuvant-induced arthritis, chronic administration of 30 mg/kg induces pulmonary damage and chronic lung inflammation.Formal Name: N-[[3'-[[(1R)-1-(4-chloro-3-methylphenyl)ethyl]amino]-3,5-dimethyl[1,1'-biphenyl]-4-yl]carbonyl]-L-alanine. CAS Number: 1233332-14-3. Molecular Formula: C27H29ClN2O3. Formula Weight: 465.0. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 25 mg/ml, DMSO: 25 mg/ml, Ethanol: 25 mg/ml, Ethanol:PBS(pH 7.2) (1:5): 0.15 mg/ml. lambdamax: 212, 249, 316 nm. SMILES: CC1=C(Cl)C=CC([C@@H](C)NC2=CC(C3=CC(C)=C(C(N[C@@H](C)C(O)=O)=O)C(C)=C3)=CC=C2)=C1. InChi Code: InChI=1S/C27H29ClN2O3/c1-15-11-20(9-10-24(15)28)18(4)29-23-8-6-7-21(14-23)22-12-16(2)25(17(3)13-22)26(31)30-19(5)27(32)33/h6-14,18-19,29H,1-5H3,(H,30,31)(H,32,33)/t18-,19+/m1/s1. InChi Key: KYHUARFFBDLROH-MOPGFXCFSA-N.