Back to the future: Oral small molecule kinases: Small molecule kinase inhibitors, what are they and how are they effective?

摘要

The treatment of RA has changed dramatically over the past century from medications addressing symptom control to DMARDs. The first recorded medication for use in rheumatism was in the late 17th century when a Peruvian bark that contains the antimalarial quinine was used in therapy. Willow bark, which contains salicylate, was introduced in 1763. In 1897 the Bayer Company introduced acetylsalicylic acid for the treatment of rheumatic disorders. Intramuscular gold was introduced in 1929, initially as a treatment for tuberculosis, but it was quickly recognized as a treatment for RA [1 ]. In 1948 Hench and Kendall [2, 3] discovered the anti-inflammatory effects of steroids. In the last half of the 20th century, a number of NSAIDs were introduced as well as synthetic oral small molecule immune-mediating medications including MTX, SSZ, penicillamine, AZA and finally LEF in 1999. All of these medications were significant advances in treating the clinical symptoms of RA and several, including gold, MTX, SSZ and LEF, have been shown to be disease modifying by inhibiting radiographic progression [4]. What do all these medications have in common? All, with the exception of injectable gold salts, are oral small molecules.