生物活性

• 描述S100 calcium-binding protein A9 (S100A9) plays an essential role in the regulation of inflammatory processes and immune responses, and has been shown to be involved in the pathogenesis of osteoarthritis. Paquinimod is an immunomodulatory compound that specifically inhibits the interaction of S100A9. The ABR22464-S100A9 interaction was competed by paquinimod in a dose-dependent manner with an IC50 value of 37 μM. Paquinimod in increasing concentrations competed for RAGE-S100A9 binding in the presence of Ca⁺⁺ and Zn⁺⁺ with an IC50 value of 26 μM. The binding of S100A9 to immobilized hTLR4/MD2 was also inhibited by paquinimod with an IC50 value of 23 μM. Mouse osteoarthritis (OA) models were developed and treated with high (collagenase-induced OA, CIOA) or low synovial activation (destabilized medial meniscus, DMM model). The administration of paquinimod at the concentration of 3.75 mg/kg in the drinking water started 4 days before the induction of the models. On day 42, CIOA mice treated by paquinimod showed significantly reduced synovial thickening at the medial size of the patella-femur region (57%). The osteophyte size was also significantly decreased at the medial femur (66%) and cruciate ligament (67%) compared to mice without paquinimod treatment. In DMM model, paquinimod only reduced the cartilage damage at the medial femur (64%) but not at the medial tibia. The osteophyte size in DMM mice was not affected by paquinimod in neither medial tiabia nor femur.
• 作用机制Paquinimod specifically inhibit the interaction of S100A9 via directly binding to S100A9.

• 动物研究
  剂量	Mice: 0.04 mg/kg - 5 mg/kg[1] (p.o.), 0.5 mg/kg - 25 mg/kg[2] (p.o.)
  给药途径	p.o.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01487551	Systemic Sclerosis	Phase 2	Completed	-	Germany ... more >> Berlin, Germany Cologne, Germany Erlangen, Germany Sweden Gothenburg, Sweden Lund, Sweden Switzerland Zürich, Switzerland Collapse <<
  NCT00997100	Systemic Lupus Erythematosus	Phase 2	Completed	-	Denmark ... more >> Soren Jacobsen Copenhagen, Denmark, 2100 Sweden Dept of Rheumatology, University Hospital in Lund Lund, Sweden, 220 07 Iva Gunnarsson M.D. Stockholm, Sweden, 171 76 Lars Rönnblom M.D. Uppsala, Sweden, 751 85 Collapse <<