ArticleJournal of clinical immunology2011
A benzamide-linked small molecule HS-Cf inhibits TNF-α-induced interferon regulatory factor-1 in porcine chondrocytes: a potential disease-modifying drug for osteoarthritis therapeutics.
Article in Journal of clinical immunology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Article
- The IRF1/GBP5 axis promotes osteoarthritis progression by activating chondrocyte pyroptosis.Journal of orthopaedic translation · 2024Article
- Small molecule inhibitors of osteoarthritis: Current development and future perspective.Frontiers in physiology · 2023Review
- NSC828779 Alleviates Renal Tubulointerstitial Lesions Involving Interleukin-36 Signaling in Mice.Cells · 2021Article
- Cf-02, a novel benzamide-linked small molecule, blunts NF-κB activation and NLRP3 inflammasome assembly and improves acute onset of accelerated and severe lupus nephritis in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- More Than Resveratrol: New Insights into Stilbene-Based Compounds.Biomolecules · 2020Review
- Arthroprotective Effects of Cf-02 Sharing Structural Similarity with Quercetin.International journal of molecular sciences · 2018Article
- Physiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory.Scientific reports · 2017Article
- Targeted inhibition of STATs and IRFs as a potential treatment strategy in cardiovascular disease.Oncotarget · 2016Review
- Metabolic syndrome and components exacerbate osteoarthritis symptoms of pain, depression and reduced knee function.Annals of translational medicine · 2016Article
- Article
- Metabolic syndrome meets osteoarthritis.Nature reviews. Rheumatology · 2012Review
- A benzamide-linked small molecule NDMC101 inhibits NFATc1 and NF-κB activity: a potential osteoclastogenesis inhibitor for experimental arthritis.Journal of clinical immunology · 2012Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUsing tumor necrosis factor-alpha (TNF-α)-activated porcine chondrocytes as a screening tool, we aim to synthesize and identify small-molecule inhibitors preserving immunomodulatory effects as therapeutics for osteoarthritis (OA).
methodsChondrocytes were isolated from pig joints. A minilibrary of 300 benzamide-linked small molecules was established. The levels of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) were measured by Western blot and Griess reaction, respectively. Proteoglycan degradation in cartilage explants was determined by histochemistry analysis. The activation of transcription factors and protein kinases was determined by electrophoretic mobility shift assays or Western blots. Zymography and real-time reverse transcriptase-polymerase chain reaction were used to determine enzyme activity and expression of matrix metalloproteinases (MMPs) and aggrecanases, respectively.
resultsBioassay screening of benzamide-linked small molecules revealed that 2-hydroxy-N-[3-(trifluoromethyl)phenyl]benzamide (HS-Cf) was a potent inhibitor of NO production and iNOS expression in TNF-α-stimulated porcine chondrocytes. HS-Cf suppressed TNF-α-induced activity of MMP-13 and expressions of several aggrecanases and prevented TNF-α-mediated reduction of collagen II. Histochemistry analysis confirmed that HS-Cf could prevent TNF-α-induced degradation and release of proteoglycan/aggrecan in cartilage explants. Such effects by HS-Cf were likely through suppressing TNF-α-induced interferon regulatory factor-1 (IRF-1) but not nuclear factor-kappaB signaling. The significance of IRF-1 was further confirmed by short hairpin knockdown studies.
conclusionsIn a minilibrary containing 300 small molecules, we identified a benzamide-linked small molecule, HS-Cf, that through down-regulating TNF-α-induced IRF-1 activity suppressed chondrocyte activation and prevented cartilage destruction. HS-Cf might be a potential disease-modifying drug for OA therapeutics.
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