Development of a selective matrix metalloproteinase 13 (MMP-13) inhibitor for the treatment of Osteoarthritis

Bendele, Alison M.; Neelagiri, Madhavi; Neelagiri, Venugopal Rao; Sucholeiki, Irving

doi:10.1016/j.ejmech.2021.113666

“…[144] Candelario et al detected the activity of MMP-9 in rat stroke brain samples using the 5-FAM/QXL 520 FRET pair. [145] The 5-FAM/QXL 520 FRET pair has also been applied in the enzymatic activity assays of various enzymes, including MMPs (MMP-1, [146] MMP-3, [147] MMP-7, [148] MMP-12, [149] MMP-13, [150] MMP-14, [151] and MMP-17 [152] ), HCV NS3 protease, [153] heart failure related resin, [154] thrombin, [155] SARS-CoV main protease 3CL pro , [156] neprilysin (NEP), [157] and fibroblast activation protein (FAP). [158] QXL 570 is also able to quench luminescent graphene oxide (GO) nanomaterials.…”

Section: Qxl Quenchersmentioning

confidence: 99%

Small‐Molecule Quenchers for Förster Resonance Energy Transfer: Structure, Mechanism, and Applications

Fang

¹

,

Shen

²

,

Peng

³

et al. 2022

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For fluorogenic probes, Förster resonance energy transfer (FRET) is one of the most widely used mechanisms to realize the detection of biochemical activities. Dark quenchers relax from the excited state to the ground state nonradiatively, and are promising alternatives to fluorescent FRET acceptors. Small-molecule (dark) quenchers have been widely used as acceptors in FRET-based probes to monitor various physiological processes with minimum background signal. Herein, we summarize the relevant advances of small-molecule quenchers that are used in FRET-based probes. This Review is intended to provide suggestions regarding the rationale design and selection of appropriate fluorophorequencher FRET pairs, which are fully compatible with challenging analytical applications in various biological systems. Finally, an outlook of the future biomedical applications and developments of this field is presented.

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“…[144] Candelario et al detected the activity of MMP-9 in rat stroke brain samples using the 5-FAM/QXL 520 FRET pair. [145] The 5-FAM/QXL 520 FRET pair has also been applied in the enzymatic activity assays of various enzymes, including MMPs (MMP-1, [146] MMP-3, [147] MMP-7, [148] MMP-12, [149] MMP-13, [150] MMP-14, [151] and MMP-17 [152] ), HCV NS3 protease, [153] heart failure related resin, [154] thrombin, [155] SARS-CoV main protease 3CL pro , [156] neprilysin (NEP), [157] and fibroblast activation protein (FAP). [158] QXL 570 is also able to quench luminescent graphene oxide (GO) nanomaterials.…”

Section: Qxl Quenchersmentioning

confidence: 99%

Small‐Molecule Quenchers for Förster Resonance Energy Transfer: Structure, Mechanism, and Applications

Fang

¹

,

Shen

²

,

Peng

³

et al. 2022

View full text Add to dashboard Cite

For fluorogenic probes, Förster resonance energy transfer (FRET) is one of the most widely used mechanisms to realize the detection of biochemical activities. Dark quenchers relax from the excited state to the ground state nonradiatively, and are promising alternatives to fluorescent FRET acceptors. Small-molecule (dark) quenchers have been widely used as acceptors in FRET-based probes to monitor various physiological processes with minimum background signal. Herein, we summarize the relevant advances of small-molecule quenchers that are used in FRET-based probes. This Review is intended to provide suggestions regarding the rationale design and selection of appropriate fluorophorequencher FRET pairs, which are fully compatible with challenging analytical applications in various biological systems. Finally, an outlook of the future biomedical applications and developments of this field is presented.

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“…A recent publication has reported the development of a new allosteric metalloproteinase-13 inhibitor, AQU-019, which has been developed as a new DMOAD. 44 Initial studies have shown promise in a rat model of OA. 44…”

Section: Future Potential Developmentsmentioning

confidence: 99%

Osteoarthritis: Advances and Emerging Treatments

Kirkham-Wilson¹,

Dennison²

2022

Rheumatology

0

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Osteoarthritis (OA) is the most common joint condition globally, affecting 10% of men and 18% of women over the age of 60. Its pathogenesis is multifactorial, which has made identifying modifiable factors to slow the progression or prevent the development of OA challenging. Current treatment focuses largely on lifestyle modification, analgesia and ultimately joint replacement, with no specific therapies currently available. However, research is on-going to provide a disease-modifying drug akin to those available for rheumatoid arthritis. The heterogeneity of OA has allowed a variety of pharmaceutical agents to be considered, each aiming to modify different components of the arthritic joint. Only a limited number of targeted treatments have been found to be efficacious, and those that have been identified have been associated with adverse events, preventing their progression to clinical practice. This article reviews the current management of OA, including tissue-specific approaches and treatments and summarizes the on-going research that aims to identify further therapeutic targets and develop disease-modifying OA drugs.

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Development of a selective matrix metalloproteinase 13 (MMP-13) inhibitor for the treatment of Osteoarthritis

Cited by 19 publications

References 46 publications

Small‐Molecule Quenchers for Förster Resonance Energy Transfer: Structure, Mechanism, and Applications

Small‐Molecule Quenchers for Förster Resonance Energy Transfer: Structure, Mechanism, and Applications

Small‐Molecule Quenchers for Förster Resonance Energy Transfer: Structure, Mechanism, and Applications

Osteoarthritis: Advances and Emerging Treatments

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