T-614 alters the production of matrix metalloproteinases (MMP-1 andMMP-3) and inhibits the migratory expansion of rheumatoid synovial fibroblasts, in vitro

Du, Fukuan; Lu, Liangjing; Teng, Jialin; Shen, Nan; Ye, Ping; Bao, Chunde

doi:10.1016/j.intimp.2012.03.003

Cited by 30 publications

(26 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Matrix metalloproteinases (MMPs) are produced by fibroblastlike synoviocytes and play an important role in the destruction and erosion of articular cartilage in RA. IGU inhibits the production of MMP-1 and MMP-3 by rheumatoid synovial fibroblasts, thereby inhibiting the invasion of fibroblast-like synoviocytes stimulated by inflammatory cytokine (Du et al, 2012). Clinical study reported that serum MMP-3 level predicted the response in RA patients with IGU and bDMARDs combined treatment .…”

Section: Preventing Cartilage Erosionmentioning

confidence: 99%

Iguratimod as a New Drug for Rheumatoid Arthritis: Current Landscape

Xie

Tian

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

Iguratimod (IGU) is a novel synthetic small molecule disease modified anti-rheumatic drug approved only in Japan and China up to date. IGU plays an important immunomodulatory role in the synovial tissue of rheumatoid arthritis by inhibiting the production of immunoglobulins and cytokines and regulating T lymphocyte subsets. IGU also regulates bone metabolism by stimulating bone formation while inhibiting osteoclast differentiation, migration, and bone resorption. In clinical trials, IGU was shown to be superior to placebo and not inferior to salazosulfapyridine. Combined therapy of IGU with other disease-modifying anti-rheumatic drugs showed significant improvements for disease activity. IGU has good efficacy and tolerance as an additional treatment for rheumatoid arthritis patients with inadequate response to methotrexate and biological disease-modifying anti-rheumatic drugs. In this review, we summarize current landscape on the mechanism of action of IGU and its clinical effectiveness and safety. It is expected that further translational studies on IGU will pave the road for wider application of IGU in the treatment of autoimmune diseases other than rheumatoid arthritis.

show abstract

Section: Preventing Cartilage Erosionmentioning

confidence: 99%

Iguratimod as a New Drug for Rheumatoid Arthritis: Current Landscape

Xie

Tian

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Iguratimod is a novel disease-modifying anti-rheumatic drug. Numerous studies have revealed that, when treated with iguratimod, the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8 and IL-17) are declined in arthritis rats, and their arthritis symptoms are also relieved (12,16,35). The current study therefore hypothesized that its anti-inflammatory effects may also enable it to alleviate bone cancer pain.…”

Section: Discussionmentioning

confidence: 99%

Anti-rheumatic drug iguratimod protects against cancer-induced bone pain and bone destruction in a rat model

Sun

Zhang

et al. 2017

Oncology Letters

View full text Add to dashboard Cite

The bone is one of the most common sites of metastasis in patients with cancer. Current treatments for bone metastases include bisphosphonates, denosumab, non-steroidal anti-inflammatory drugs and analgesics, but each of them has certain limitations. Cytokines and mediators released from various cells in the bone microenvironment may drive a vicious cycle of osteolytic bone metastases. Iguratimod (T-614), a novel disease-modifying anti-rheumatic drug, has demonstrated therapeutic effects by suppressing the production of inflammatory cytokines in rats and patients with rheumatoid arthritis. Therefore, the current study evaluated the hypothesis that iguratimod may protect against cancer-induced bone pain and bone metastasis in a rat model. For this purpose, rats inoculated with Walker 256 cells were treated with iguratimod from days 11–17 post-surgery. Mechanical paw withdrawal thresholds and expression levels of phosphorylated extracellular signal-related kinase (pERK) and c-Fos in the spinal cord were investigated to detect changes in bone pain. Bone destruction levels were detected using X-rays, hematoxylin and eosin and tartrate-resistant acid phosphatase staining. The results revealed that mechanical paw withdrawal thresholds and the expression levels of pERK and c-Fos declined in a dose-dependent manner in rats treated with iguratimod, and bone destruction severity was also reduced. These findings may provide important new insights into the treatment of bone metastasis symptoms.

show abstract

“…The pathophysiological mechanisms of radiographic nonprogression in RA patients treated with various DMARDs remain uncertain. A csDMARD, IGU, inhibits the production of proinflammatory cytokines including TNF-α, IL-1B, IL-6, IL-8, IL-17, MCP-1 [2][3][4][5][6][7][8][9], and the MMP-1 and MMP-3 [11,12] which play a pivotal role in the structural destruction in RA. [13][14][15].…”

Section: Safetymentioning

confidence: 99%

“…Iguratimod (IGU) in animal and in vitro studies demonstrates its antirheumatic actions and inhibitory effects on structural damage as follows: (1) antiinflammatory and analgesic effects [1]; (2) inhibition of various cytokines production including interleukin (IL)-1β, IL-6, IL-17, tumor necrosis factor-α (TNF-α) [2][3][4][5][6][7], and inhibition of the production of immunoglobulins [8]; (3) prevention of bone/cartilage destruction and inflammation in collagen-induced arthritis in rats [7] and mice [9]; (4) stimulation of osteoblastic differentiation and of bone morphogenetic protein-2-induced bone formation [10]; (5) inhibition of the production of matrix metalloproteinase (MMP)-1 and MMP-3, which play a pivotal role in the structural destruction in RA [11]; (6) inhibition of nuclear factor-kappaB (NF-κB) activation [5,6], promoting production of various cytokines, and monocyte chemoattractant protein-1 (MCP-1) [3,5]; and (7) suppression of the production of the receptor activator of NF-κB ligand (RANKL) playing a role in osteoclastogenesis, bone resorption, and structural damage, and IL-17 and MMP-3 expression [12]. IGU (N- amino]-4-oxo-6-phenoxy-4H-1-benzopyran-3-yl] formamide, C 17 H 14 N 2 O 6 S) is classified as a conventional sDMARD (csDMARD) but not as a targeted synthetic (ts) DMARD (JAK inhibitor).…”

Section: Introductionmentioning

confidence: 99%

Iguratimod, A Synthetic Disease Modifying Anti- Rheumatic Drug (Sdmard), and Various Dmards Suppress Joint Destruction. The Pathophysiological Mechanisms of the Inhibition of Bone/Cartilage Destruction

Ishikawa¹,

Ishikawa²

2018

Journal of Bone Biology and Osteoporosis

View full text Add to dashboard Cite

Objective: To elucidate the radiographic outcomes for rheumatoid arthritis (RA) patients using the synthetic disease-modifying antirheumatic drug (sDMARD) Iguratimod (IGU) and other DMARDs including injectable sodium aurothiomalate, bucillamine, salazosulphapyridine, infliximab, etanercept, tocilizumab and/or abatacept.Patients and Methods: 213 patients were enrolled in this study. Total Genant-modified Sharp scores (GSS) of hands/wrists and feet at baseline and at week 104 were calculated in 31 RA patients treated with a daily dose of 25 mg or 50 mg for 104 weeks.Results: Total GSS of 31 patients at week 104 showed no progression (total GSS <= 0.84: the smallest detectable change) in 16 (52%) patients with a mean score reduction (95% CI) of-4.3 (-8.1 ~ -0.5) (p < 0.05).Conclusion: Treatment with the sDMARD, IGU showed no radiographic progression in 16 (52%) RA patients at week 104. Concerning the suppression mechanism of joint destruction by IGU and other DMARDs, we speculate that DMARDs prevent bone/cartilage destruction by inhibiting the receptor activator of nuclear factor-kappa B (NF- kB) lig and (RANKL) and through other antirheumatic actions.

show abstract

T-614 alters the production of matrix metalloproteinases (MMP-1 andMMP-3) and inhibits the migratory expansion of rheumatoid synovial fibroblasts, in vitro

Cited by 30 publications

References 25 publications

Iguratimod as a New Drug for Rheumatoid Arthritis: Current Landscape

Iguratimod as a New Drug for Rheumatoid Arthritis: Current Landscape

Anti-rheumatic drug iguratimod protects against cancer-induced bone pain and bone destruction in a rat model

Iguratimod, A Synthetic Disease Modifying Anti- Rheumatic Drug (Sdmard), and Various Dmards Suppress Joint Destruction. The Pathophysiological Mechanisms of the Inhibition of Bone/Cartilage Destruction

Contact Info

Product

Resources

About