NIBR 0213

Product NameNIBR 0213
CAS1233332-14-3
MFC27H29ClN2O3
MW464.98
EINECS
MOL File1233332-14-3.mol

Chemical Properties

storage temp.	Store at -20°C
solubility	DMF: 25 mg/ml; DMSO: 25 mg/ml; Ethanol: 25 mg/ml; Ethanol:PBS(pH 7.2) (1:5): 0.15 mg/ml
form	A crystalline solid
color	Off-white to light yellow
InChIKey	KYHUARFFBDLROH-MOPGFXCFSA-N
SMILES	C(O)(=O)[C@H](C)NC(C1=C(C)C=C(C2=CC=CC(N[C@@H](C3=CC=C(Cl)C(C)=C3)C)=C2)C=C1C)=O

Safety Information

WGK Germany	WGK 3
Storage Class	11 - Combustible Solids

Usage And Synthesis

Uses

NIBR 0213 is a potent and selective inhibitor of sphingosine 1-phosphate receptor-1 (S1P1), a G protein-coupled receptor that has been highlighted as a promising therapeutic target in autoimmunity disorders.

Biological Activity

NIBR-0213 is an orally active, potent and S1P1-selective sphingosine 1-phosphate (S1P) receptor antagonist th at blocks S1P1-selective ligand AUY954-induced Ca2+ mobilization (IC50 = 2.5 nM using human S1P1-transfected HeLa cells; IC50 >10 μM with human S1P2, S1P3, or S1P4 transfectants) and S1P-induced GTPγS recruitment (IC50 = 2.0/2.3/8.5 nM using membrane from human/murine/r at S1P1-transfected CHO cells; IC50 >10 μM with membrane from human S1P5 transfectant). NIBR-0213 induces long-lasting peripheral blood lymphocyte reduction in rats (EDmax = 1 mg/kg, ED50 = 0.2 mg/kg; p.o.) and exhibits therapeutic efficacy (30 mg/kg p.o; BID) in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), with no adverse effects to the animals.

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].

Animal Model:	Lewis or Wistar rats (220-250 g, males)^[1]
Dosage:	30mg/kg
Administration:	Orally
Result:	Reduced the PBL counts by 75%-85% within 14hr and maintained this effect up to 24hr posttreatment.

Animal Model:	C57BL/6 mice bearing EAE model^[1]
Dosage:	30mg/kg and 60mg/kg
Administration:	30mg/kg twice per day (BID) for 3days and then increased to 60mg/kg BID until the remainder of the experiment. In total, the treatment lasted 26days
Result:	Resulted in a gradual reduction in disease-scores, with a divergence from vehicle controls that became significant after 5days.

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