NIBR0213

NIBR-0213 is a potent, orally active and selective S1P1 antagonist with efficacy in experimental autoimmune encephalomyelitis. NIBR-0213 displays potent and comparable potency on human and rat S1P1 (IC₅₀ of 2.0 nM and 2.3 nM, respectively) in GTPγ³⁵S assays^[1]. In Vitro:NIBR-0213 displays an inhibitory activity on hS1P1 with an IC₅₀ of 2.5 nM whereas it is inactive (IC₅₀ >10 μM) on S1P2, S1P3, and S1P4 in Ca²⁺ mobilization assays^[1].
NIBR-0213 displays potent and comparable potency on human and rat S1P1 (IC₅₀ of 2.0 nM and 2.3 nM, respectively) in GTPγ³⁵S assays, whereas on mouse S1P1 with an IC₅₀ of 8.5 nM^[1].
NIBR-0213 shows an about 3,000-fold selectivity against human S1P5 in the GTPγ³⁵S assay^[1].
NIBR-0213 is a competitive S1P1 antagonist with a calculated K_d of 0.37±0.031 nM^[1]. In Vivo:NIBR-0213 (given orally at 30 mg/kg to rats) reduces the peripheral blood lymphocyte (PBL) counts by 75%-85% within 14 hr and maintained this effect up to 24 hr posttreatment^[1].
NIBR-0213 (30 mg/kg and 60 mg/kg) is efficacious when given therapeutically in a mouse experimental autoimmune encephalomyelitis (EAE) model^[1].
The PK properties of NIBR-0213 shows a moderate clearance (26 mL/min/kg) and a high oral bioavailability (69%), leading to significant exposure after oral dosing^[1].