ArticleChemMedChem2008
Zinc-binding groups modulate selective inhibition of MMPs.
Article in ChemMedChem, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 140 citations in OpenAlex.
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- The role and mechanisms of matrix metalloproteinase-9 in peripheral neuropathic pain.Frontiers in molecular neuroscience · 2025Review
- Boronate-Based Bioactive Compounds Activated by Peroxynitrite and Hydrogen Peroxide.Redox biochemistry and chemistry · 2024Article
- Emerging Trends and Innovations in the Treatment and Diagnosis of Atherosclerosis and Cardiovascular Disease: A Comprehensive Review towards Healthier Aging.Pharmaceutics · 2024Review
- MMP-9-dependent proteolysis of the histone H3 N-terminal tail: a critical epigenetic step in driving oncogenic transcription and colon tumorigenesis.Molecular oncology · 2024Article
- Effects of barakol fromHeliyon · 2024Article
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Chondroitin Sulfate Proteoglycan 4 as a Marker for Aggressive Squamous Cell Carcinoma.Cancers · 2022Review
- Hydroxypyrone derivatives in drug discovery: from chelation therapy to rational design of metalloenzyme inhibitors.RSC medicinal chemistry · 2022Review
- The Screening of Therapeutic Peptides for Anti-Inflammation through Phage Display Technology.International journal of molecular sciences · 2022Review
- Structure-Based Design of α-Substituted Mercaptoacetamides as Inhibitors of the Virulence Factor LasB fromACS infectious diseases · 2022Article
- MMP9: A Tough Target for Targeted Therapy for Cancer.Cancers · 2022Review
- MMP-9 drives the melanomagenic transcription program through histone H3 tail proteolysis.Oncogene · 2022Article
- Reversion inducing cysteine rich protein with Kazal motifs and cardiovascular diseases: The RECKlessness of adverse remodeling.Cellular signalling · 2021Review
- Role of Matrix Metalloproteinases in Angiogenesis and Its Implications in Asthma.Journal of immunology research · 2021Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The need for selective matrix metalloproteinase (MMP) inhibition is of interest because of the range of pathologies mediated by different MMP isoforms. The development of more selective MMP inhibitors (MMPi) may help to overcome some of the undesired side effects that have hindered the clinical success of these compounds. In an effort to devise new approaches to selective inhibitors, herein we describe several novel MMPi and show that their selectivity is dependent on the nature of the zinc-binding group (ZBG). This is in contrast to most current MMPi, which obtain isoform selectivity solely from the peptidomimetic backbone portion of the compound. In the present study, six different hydroxypyrone and hydroxypyridinone ZBGs were appended to a common biphenyl backbone and the inhibition efficiency of each inhibitor was determined in vitro (IC(50) values) against MMP-1, -2, -3, -7, -8, -9, -12, and -13. The results show that the selectivity profile of each inhibitor is different as a result of the various ZBGs. Computational modeling studies were used to explain some trends in the observed selectivity profiles. To assess the importance of the ZBG in a biological model, two of the semiselective, potent MMPi (and one control) were evaluated using an isolated perfused rat heart system. Hearts were subjected to ischemia reperfusion injury, and recovery of contractile function was examined. In this model, only one of the two MMPi showed significant and sustained heart recovery, demonstrating that the choice of ZBG can have a significant effect in a relevant pathophysiological endpoint.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.