Matrix metalloproteinases and inhibitors in dentistry

Boelen, Gerd-Jan; Boute, Lucas; d'Hoop, Joëy; EzEldeen, Mostafa; Lambrichts, Ivo; Opdenakker, Ghislain

doi:10.1007/s00784-019-02915-y

Cited by 66 publications

(64 citation statements)

References 68 publications

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“…There is an established history of clinically successful MMP inhibitors. Periostat, which is doxycycline (Figure 4) formulated at a sub-antimicrobial dose, is a U.S. Food and Drug Administration (FDA)-approved MMP inhibitor for periodontal disease treatment [201,202,203,204]. Doxycycline is a broad-spectrum MMP inhibitor with IC 50 values in the range of 2–50 μM [18].…”

Section: The Outlook For Current Mmp Inhibitorsmentioning

confidence: 99%

The Rebirth of Matrix Metalloproteinase Inhibitors: Moving Beyond the Dogma

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2019

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The pursuit of matrix metalloproteinase (MMP) inhibitors began in earnest over three decades ago. Initial clinical trials were disappointing, resulting in a negative view of MMPs as therapeutic targets. As a better understanding of MMP biology and inhibitor pharmacokinetic properties emerged, it became clear that initial MMP inhibitor clinical trials were held prematurely. Further complicating matters were problematic conclusions drawn from animal model studies. The most recent generation of MMP inhibitors have desirable selectivities and improved pharmacokinetics, resulting in improved toxicity profiles. Application of selective MMP inhibitors led to the conclusion that MMP-2, MMP-9, MMP-13, and MT1-MMP are not involved in musculoskeletal syndrome, a common side effect observed with broad spectrum MMP inhibitors. Specific activities within a single MMP can now be inhibited. Better definition of the roles of MMPs in immunological responses and inflammation will help inform clinic trials, and multiple studies indicate that modulating MMP activity can improve immunotherapy. There is a U.S. Food and Drug Administration (FDA)-approved MMP inhibitor for periodontal disease, and several MMP inhibitors are in clinic trials, targeting a variety of maladies including gastric cancer, diabetic foot ulcers, and multiple sclerosis. It is clearly time to move on from the dogma of viewing MMP inhibition as intractable.

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Section: The Outlook For Current Mmp Inhibitorsmentioning

confidence: 99%

The Rebirth of Matrix Metalloproteinase Inhibitors: Moving Beyond the Dogma

Fields

2019

Cells

248

212

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“…Zinc administered together with its ionophore would contribute to increased intracellular zinc. Intracellular zinc would inhibit RNAdependent RNA polymerase (RdRp) of the virus Tetracyclines are well-known MMPs inhibitors (Boelen et al, 2019;Castro, Kandasamy, Youssef, & Schulz, 2011), but the direct relationship between MMPs and SARS-CoV-2 has yet to be examined.…”

Section: The Proposed Mechanism Of Action Of Drugs Targeting Zinc Omentioning

confidence: 99%

“…Tetracyclines are well‐known MMPs inhibitors (Boelen et al, 2019; Castro, Kandasamy, Youssef, & Schulz, 2011), but the direct relationship between MMPs and SARS‐CoV‐2 has yet to be examined.…”

Section: Drugs Targeting Zinc and Mers‐cov Sars‐cov And Sars‐cov‐2mentioning

confidence: 99%

Targeting zinc metalloenzymes in coronavirus disease 2019

Doboszewska

Właź

Nowak

et al. 2020

British J Pharmacology

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Several lines of evidence support a link between the essential element zinc and the coronavirus disease 2019 (COVID-19). An important fact is that zinc is present in proteins of humans and of viruses. Some zinc sites in viral enzymes may serve as drug targets and may liberate zinc ions, thus leading to changes in intracellular concentration of zinc ions, while increased intracellular zinc may induce biological effects in both the host and the virus. Drugs such as chloroquine may contribute to increased intracellular zinc. Moreover, clinical trials on the use of zinc alone or in addition to other drugs in the prophylaxis/treatment of COVID-19 are ongoing. Thereby, we aim to discuss the rationale for targeting zinc metalloenzymes as a new strategy for the treatment of COVID-19.

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“…[11][12][13][14] These efforts suffer from key disadvantages, which require more efficient strategies and novel technologies in contemporary dentistry. [15][16][17][18] Nanoparticles, unlike other biomaterials, present distinct biological properties and can be used in novel applications in restorative dentistry, prosthetic dentistry, endodontics, implantology, oral cancers, and periodontology. Nanoparticles have immense potential because of their antimicrobial, antiviral, and antifungal properties.…”

Section: Introductionmentioning

confidence: 99%