Successful treatment of animal models of rheumatoid arthritis with small-molecule cyclin-dependent kinase inhibitors.

Cyclin-Dependent Kinase Inhibitors Rheumatoid Arthritis with Small-Molecule Successful Treatment of Animal Models of

Adenoviral transfer of cyclin-dependent kinase inhibitor genes suppresses collagen-induced arthritis in mice.

In rheumatoid synovial tissues, synovial fibroblasts are activated by proinflammatory cytokines and proliferate to develop hyperplastic pannus tissues, which irreversibly damage the affected joints. We recently reported that the cyclin-dependent kinase inhibitors p16(INK4a) and p21(Cip1) are not expressed in vivo in rheumatoid synovial fibroblasts, but are readily inducible in vitro. This obser...

3D-QSAR and docking analysis on a series of multi-cyclin-dependent kinase inhibitors using CoMFA, and CoMSIA

A series of 42 Pyrazolo[4,3-h]quinazoline-3-carboxamides as multi-cyclin-dependent kinaseinhibitors regarded as promising antitumor agents to complement the existing therapies, wassubjected to a three-dimensional quantitative activity relationship (3D QSAR). Different QSARmethods, comparative molecular field analysis (CoMFA), CoMFA region focusing, andcomparative molecular similarity indices an...

Inhibition of CDK9 as a therapeutic strategy for inflammatory arthritis

Rheumatoid arthritis is characterised by synovial inflammation and proliferation of fibroblast-like synoviocytes. The induction of apoptosis has long been proposed as a target for proliferative autoimmune diseases, and has further been shown to act as a successful treatment of experimental models of arthritis, such as collagen-induced arthritis. Here we examined the effects of specific oral sma...

B-cell kinase inhibitors in rheumatoid arthritis

Introduction The pathogenesis of rheumatoid arthritis (RA) involves systemic dysregulation of T and B lymphocytes resulting in immune responses against self-antigens, and ultimately leading to downstream effects such as cartilage destruction, pannus formation, and bone erosion. Clinical evidence for the role of B cells in RA includes the effectiveness of rituximab, an antibody designed to deple...