Identification of small molecule inhibitors against MMP-14 via High-Throughput screening

Lee, Hyun; Youn, Isoo; Demissie, Robel; Vaid, Tasneem M.; Che, Chun‐Tao; Azar, Dimitri T.; Han, Kyu-Yeon

doi:10.1016/j.bmc.2023.117289

Cited by 3 publications

(3 citation statements)

References 56 publications

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“…The researchers believe that ND-336 and related compounds could be used to treat cancer [11]. method, which involves testing large numbers of small molecules as potential MMP-14 inhibitors [228].…”

Section: Mmp-14 Inhibitorsmentioning

confidence: 99%

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Matrix Metalloproteinases Inhibitors in Cancer Treatment: An Updated Review (2013–2023)

Almutairi,

Kalloush,

Manoon

et al. 2023

Molecules

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Matrix metalloproteinases (MMPs) are identifiable members of proteolytic enzymes that can degrade a wide range of proteins in the extracellular matrix (ECM). MMPs can be categorized into six groups based on their substrate specificity and structural differences: collagenases, gelatinases, stromelysins, matrilysins, metalloelastase, and membrane-type MMPs. MMPs have been linked to a wide variety of biological processes, such as cell transformation and carcinogenesis. Over time, MMPs have been evaluated for their role in cancer progression, migration, and metastasis. Accordingly, various MMPs have become attractive therapeutic targets for anticancer drug development. The first generations of broad-spectrum MMP inhibitors displayed effective inhibitory activities but failed in clinical trials due to poor selectivity. Thanks to the evolution of X-ray crystallography, NMR analysis, and homology modeling studies, it has been possible to characterize the active sites of various MMPs and, consequently, to develop more selective, second-generation MMP inhibitors. In this review, we summarize the computational and synthesis approaches used in the development of MMP inhibitors and their evaluation as potential anticancer agents.

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Section: Mmp-14 Inhibitorsmentioning

confidence: 99%

“…Virtual screening methods were also used to develop MMP-14 inhibitors [ 227 ]. Another way to discover inhibitors of MMP-14 is the high-throughput screening method, which involves testing large numbers of small molecules as potential MMP-14 inhibitors [ 228 ].…”

Section: Matrix Metalloprotease-14 (Mmp-14)mentioning

confidence: 99%

Matrix Metalloproteinases Inhibitors in Cancer Treatment: An Updated Review (2013–2023)

Almutairi,

Kalloush,

Manoon

et al. 2023

Molecules

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“…These compounds were discovered through the screening of the proteolytic activity on VEGFR peptides. Both of these compounds bind to the tunnel structure that resides in the Ω-loop region of the catalytic domain [120]. While chloroxine shows affinity against MMP-9 and MMP-13 as well, clioquinol is highly specific to MT1-MMP.…”

Section: Artificial Inhibitors Of Mt1-mmpmentioning

confidence: 99%

MT1-MMP as a Key Regulator of Metastasis

Tanaka,

Sakamoto

2023

Cells

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Membrane type1-matrix metalloproteinase (MT1-MMP) is a member of metalloproteinases that is tethered to the transmembrane. Its major function in cancer progression is to directly degrade the extracellular matrix components, which are mainly type I–III collagen or indirectly type IV collagen through the activation of MMP-2 with a cooperative function of the tissue inhibitor of metalloproteinase-2 (TIMP-2). MT1-MMP is expressed as an inactive form (zymogen) within the endoplasmic reticulum (ER) and receives truncation processing via furin for its activation. Upon the appropriate trafficking of MT1-MMP from the ER, the Golgi apparatus to the cell surface membrane, MT1-MMP exhibits proteolytic activities to the surrounding molecules such as extracellular matrix components and cell surface molecules. MT1-MMP also retains a non-proteolytic ability to activate hypoxia-inducible factor 1 alpha (HIF-1A) via factors inhibiting the HIF-1 (FIH-1)-Mint3-HIF-1 axis, resulting in the upregulation of glucose metabolism and oxygen-independent ATP production. Through various functions of MT1-MMP, cancer cells gain motility on migration/invasion, thus causing metastasis. Despite the long-time efforts spent on the development of MT1-MMP interventions, none have been accomplished yet due to the side effects caused by off-target effects. Recently, MT1-MMP-specific small molecule inhibitors or an antibody have been reported and these inhibitors could potentially be novel agents for cancer treatment.

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Optimizing drug discovery: Surface plasmon resonance techniques and their multifaceted applications

Acharya,

Behera,

Behera

2024

Chemical Physics Impact

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Identification of small molecule inhibitors against MMP-14 via High-Throughput screening

Cited by 3 publications

References 56 publications

Matrix Metalloproteinases Inhibitors in Cancer Treatment: An Updated Review (2013–2023)

Matrix Metalloproteinases Inhibitors in Cancer Treatment: An Updated Review (2013–2023)

MT1-MMP as a Key Regulator of Metastasis

Optimizing drug discovery: Surface plasmon resonance techniques and their multifaceted applications

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