Orally active S100A9 (Calgranulin B; MRP14) blocker with in vivo efficacy in murine models of autoimmune diseases.
Paquinimod (ABR-215757) is an orally active quinoline-3-carboxamide (Q substance) class immunomodulator that targets S100A9 (Calgranulin B; MRP14) via direct binding and blocks its interaction with receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (IC50 = 26 μM & 23 μM against 100 nM hS100A9 from binding immobilized hRAGE & hTLR4/MD2, respectively). Paquinimod in vivo efficacy is demonstrated in murine models of autoimmune/inflammatory diseases, including liver fibrosis, collagen-induced osteoarthritis, peritonitis, EAE, type 1 diabetes, lupus (0.04-25 mg/kg/day p.o.), and atherosclerosis (10 mg/kg i.p.).
Journal of neuroinflammation, 15(1), 252-252 (2018-09-06)
Depression is one of the most common mental disorders characterized mainly by low mood and loss of interest or pleasure. About a third of patients with depression do not respond to classic antidepressant treatments. Recent evidence suggests that Mrp8/14 (myeloid-related
International immunopharmacology, 4(12), 1515-1523 (2004-09-08)
Autoimmune, lupus-prone MRL lpr/lpr mice were treated orally with oxo-quinoline-3-carboxamide (ABR-25757), a newly developed immunomodulator. Treatment was initiated in one set of experiment at the age of 10 weeks, before the onset of clinically apparent disease, and in another set
International immunopharmacology, 18(2), 290-297 (2013-12-29)
Quinoline-3-carboxamides (Q-compounds) are currently in clinical development for both autoimmune disease and cancer. We have previously shown that the Q-compound paquinimod (ABR-215757) significantly ameliorates disease symptoms in several mouse models of human inflammatory disease. Considering that recruitment of inflammatory cells
Journal of medicinal chemistry, 47(8), 2075-2088 (2004-04-02)
Roquinimex-related 3-quinolinecarboxamide derivatives were prepared and evaluated for treatment of autoimmune disorders. The compounds were tested in mice for their inhibitory effects on disease development in the acute experimental autoimmune encephalomyelitis model and selected compounds in the beagle dog for
There is an emerging widespread interest in the role of damage-associated molecular pattern molecules (DAMP) S100A8, S100A9 and S100A12 in cardiovascular and other diseases. In this study we tested the efficacy of ABR-215757, a S100 protein binding immuno-modulatory compound to
