Protein kinase small molecule inhibitors for rheumatoid arthritis: Medicinal chemistry/clinical perspectives  

作　　者：Charles J Malemud David E Blumenthal 

机构地区：[1]The Arthritis Research Laboratory, Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve University, Cleveland, OH 44106-5076, United States [2]Department of Anatomy, Case Western Reserve University, Cleveland, OH 44106-5076, United States [3]School of Medicine, Division of Rheumatology, Veteran’s Administration Medical Center, Cleveland, OH 44106, United States

出　　处：《World Journal of Orthopedics》2014年第4期496-503,共8页世界骨科杂志（英文版）

基　　金：Supported by A contract from Genentech/Roche Group and the Case Western Reserve University School of Medicine Visual Sciences Research Core,No.P30 EY-011373

摘　　要：Medicinal chemistry strategies have contributed to the development, experimental study of and clinical trials assessment of the first type of protein kinase small molecule inhibitor to target the Janus kinase/Signal Transducers and Activators of Transcription(JAK/STAT) signaling pathway. The orally administered small molecule inhibitor, tofacitinib, is the first drug to target the JAK/STAT pathway for entry into the armamentarium of the medical therapy of rheumatoid arthritis. The introduction of tofacitinib into general rheumatologic practice coupled with increasing understanding that additional cellular signal transduction pathways including the mitogen-activated protein kinase and phosphatidylinositide-3-kinase/Akt/mammalian target of rapa-mycin pathways as well as spleen tyrosine kinase also contribute to immune-mediated inflammatory in rheumatoid arthritis makes it likely that further development of orally administered protein kinase small molecule inhibitors for rheumatoid arthritis will occur in the near future.Medicinal chemistry strategies have contributed to the development, experimental study of and clinical trials assessment of the first type of protein kinase small molecule inhibitor to target the Janus kinase/Signal Transducers and Activators of Transcription(JAK/STAT) signaling pathway. The orally administered small molecule inhibitor, tofacitinib, is the first drug to target the JAK/STAT pathway for entry into the armamentarium of the medical therapy of rheumatoid arthritis. The introduction of tofacitinib into general rheumatologic practice coupled with increasing understanding that additional cellular signal transduction pathways including the mitogen-activated protein kinase and phosphatidylinositide-3-kinase/Akt/mammalian target of rapa-mycin pathways as well as spleen tyrosine kinase also contribute to immune-mediated inflammatory in rheumatoid arthritis makes it likely that further development of orally administered protein kinase small molecule inhibitors for rheumatoid arthritis will occur in the near future.

关 键 词：CLINICAL trials Protein KINASE Signal TRANSDUCTION Small molecule inhibitor RHEUMATOID ARTHRITIS 

分 类 号：R593.22[医药卫生—内科学]