NIBR-0213 是一种有效的选择性S1P1拮抗剂，对实验性自身免疫性脑脊髓炎有效。在 GTPγ35S 试验中，NIBR-0213 有效作用于人和大鼠S1P1，IC50分别为 2.0 nM 和 2.3 nM。
| 生物活性 | NIBR-0213 is a potent and selectiveS1P1 antagonist with efficacy in experimental autoimmune encephalomyelitis. NIBR-0213 displays potent and comparable potency onhuman and rat S1P1 (IC50 of 2.0 nM and 2.3 nM, respectively) in GTPγ35S assays[1]. |
体外研究
(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 ~3,000-fold selectivity against human S1P5 in the GTPγ35S assay[1].
NIBR-0213 is a competitive S1P1 antagonist with a calculated Kd of 0.37±0.031 nM[1].
|
体内研究
(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: | 30 mg/kg | | Administration: | Orally | | Result: | Reduced the PBL counts by 75%-85% within 14 hr and maintained this effect up to 24 hr posttreatment. |
| Animal Model: | C57BL/6 mice bearing EAE model[1] | | Dosage: | 30 mg/kg and 60 mg/kg | | Administration: | 30 mg/kg twice per day (BID) for 3 days and then increased to 60 mg/kg BID until the remainder of the experiment. In total, the treatment lasted 26 days | | Result: | Resulted in a gradual reduction in disease-scores, with a divergence from vehicle controls that became significant after 5 days. |
|
| 分子量 | |
| Formula | |
| CAS 号 | |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
