Histone deacetylase inhibitors: new hope for rheumatoid arthritis?
Histone deacetylase (HDAC) inhibitors are a new family of anti-cancer agents currently undergoing clinical investigations for various oncology indications. Their anti-inflammatory activities had been well documented and they appear to be potential therapeutic strategies for various inflammatory diseases. In this review, the anti-inflammatory activities of HDAC inhibitors with emphasis on their potential applications in rheumatoid arthritis (RA) will be summarized. The possible anti-rheumatic mechanisms, including growth arrest in rheumatoid arthritis synovial fibroblasts (RASFs), suppression of pro-inflammatory cytokines or chemokines, anti-angiogenesis as well as protective effects on bone and cartilage destruction will also be discussed. Current literatures strongly imply HDAC inhibitors as innovative anti-rheumatic drug candidates. However, long-term safety is a major concern. Future investigations should focus on identification of molecular anti-rheumatic mechanisms, development of new classes of HDAC inhibitors with better safety and selectivity profiles, combination of HDAC inhibitors with disease modifying anti-rheumatic drugs (DMARDs) and establishment of topical or intra-articular formulations.
Choo
Q Y
QY
Department of Pharmacy National University of Singapore 10 Kent Ridge Crescent Singapore 119260.
Ho
P C
PC
Lin
H S
HS
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors; D006801:Humans
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D056572:Histone Deacetylase Inhibitors