NK95806, a newly synthesized microtubule-disrupting agent that suppresses collagen-induced arthritis in mice.
We investigated the anti-arthritic effects of NK95806, a novel inhibitor of microtubule polymerization, on collagen-induced arthritis in mice. The suppressive effect of NK95806 on the induction and development of arthritis was shown as a significant reduction in clinical arthritis scores. Histological analysis of the hind paws confirmed the improvement in clinical severity and showed marked decreases in granulomatous formation and further bone destruction. Further, under the experimental conditions in which methotrexate had little, if any, effect, NK95806 significantly suppressed the development of arthritis. These results suggest that the disruption of microtubules might be a novel target for anti-rheumatic drugs and NK95806 may be a candidate for further development.
Morohashi
Hirohisa
H
R&D division, Pharmaceutical group, Nippon Kayaku Co., Ltd., 31-12 Shimo 3-chome, Kita-ku, Tokyo, 115-8588 Japan.
Abe
Fuminori
F
Saiga
Kan
K
Toyoda
Eriko
E
Ichimura
Eiji
E
Nishikawa
Kiyohiro
K
D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D024043:Collagen Type II / Q000276:immunology*; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D007555:Isoxazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007596:Joints / Q000187:drug effects / Q000473:pathology; D035002:Lower Extremity / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008870:Microtubules / Q000187:drug effects*; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D000096926:Benzenesulfonamides
D018501:Antirheumatic Agents; D024043:Collagen Type II; D007555:Isoxazoles; D013449:Sulfonamides; C497709:N-(2-(4-methoxybenzenesulfonamide)phenyl)-3,5-dimethyl-4-isoxazolcarboxamide; D000096926:Benzenesulfonamides