Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Discovery of Selective Small Molecular TACE Inhibitors for the Treatment of Rheumatoid Arthritis

Author(s): N. -G. Li, Z. -H. Shi, Y. -P. Tang, Wei-Li, Lian-Yin and J. -A. Duan

Volume 19 , Issue 18 , 2012

Page: [2924 - 2956] Pages: 33

DOI: 10.2174/092986712800672120

Price: $65


Rheumatoid arthritis (RA) is a chronic, inflammatory disease that afflicts 1-2% of the world population, characterized by an immune mediated inflammatory synovitis that leads to joint destruction, functional impairment, and reduced quality of life. The treatment goals of RA should be longterm substantial relief of pain, arrested joint inflammation and damage, and improved function. Current treatment can be divided into four classes, namely general analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease modifying anti-rheumatic drugs (DMARDs) and biological agents (tumor-necrosis factor modifiers). However, gastrointestinal (GI) side effects of NSAIDs cannot be neglected, direct joint injections of glucocorticoids cannot be injected more than once every 3 months, synthetic DMARDs is far from optimal and only minority of patients achieved longterm remission, the biologics are very expensive to manufacture, need to be injected, and can cause allergic reactions. An alternative and good approach to the treatment of this disease is to lower the levels of tumour necrosis factor-α (TNF-α) in RA, which can be achieved by selectively inhibiting the tumour necrosis factor-α converting enzyme (TACE) that generate these cytokines using cheaper small molecules. This review focuses on the current status of selective small molecule inhibitors of TACE, with respect to lead compound search, inhibitors design approach, structure-activity relationship (SAR) and pharmacological studies in animals and humans. Through these methods, new hope is emerging for the treatment of RA through selective inhibition of TACE.

Keywords: Rheumatoid arthritis, inflammatory disease, tumour necrosis factor-α converting enzyme, design, synthesis, zinc binding group, matrix metalloproteinases, structure-activity relationship, selective inhibitors, pharmacokinetic

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy