scholarly journals Bone-Seeking Matrix Metalloproteinase Inhibitors for the Treatment of Skeletal Malignancy

2020 ◽  
Vol 13 (6) ◽  
pp. 113
Author(s):  
Antonio Laghezza ◽  
Luca Piemontese ◽  
Leonardo Brunetti ◽  
Alessia Caradonna ◽  
Mariangela Agamennone ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Matrix Metalloproteinases ◽  
Matrix Metalloproteinase ◽  
Bone Remodeling ◽  
Cancer Progression ◽  
Tumor Invasion ◽  
Standard Care ◽  
Computational Analysis ◽  
Matrix Metalloproteinase Inhibitors ◽  
Metalloproteinase Inhibitors

Matrix metalloproteinases (MMPs) are a family of enzymes involved at different stages of cancer progression and metastasis. We previously identified a novel class of bisphosphonic inhibitors, selective for MMPs crucial for bone remodeling, such as MMP-2. Due to the increasing relevance of specific MMPs at various stages of tumor malignancy, we focused on improving potency towards certain isoforms. Here, we tackled MMP-9 because of its confirmed role in tumor invasion, metastasis, angiogenesis, and immuno-response, making it an ideal target for cancer therapy. Using a computational analysis, we designed and characterized potent MMP-2/MMP-9 inhibitors. This is a promising approach to develop and clinically translate inhibitors that could be used in combination with standard care therapy for the treatment of skeletal malignancies.

Structure-based molecular insights into matrix metalloproteinase inhibitors in cancer treatments

2021 ◽  
pp. 00-00
Author(s):  
Haili Lin ◽  
Peng Xu ◽  
Mingdong Huang
Keyword(s):  
Clinical Trials ◽  
Matrix Metalloproteinases ◽  
Matrix Metalloproteinase ◽  
Protease Inhibitors ◽  
Anticancer Agents ◽  
Cancer Development ◽  
Pharmaceutical Companies ◽  
Matrix Metalloproteinase Inhibitors ◽  
Cancer Treatments ◽  
Metalloproteinase Inhibitors

Protease inhibitors are of considerable interest as anticancer agents. Matrix metalloproteinases (MMPs) were the earliest type of proteases considered as anticancer targets. The developments of MMP inhibitors (MMPIs) by pharmaceutical companies can be dated from the early 1980s. Thus far, none of the over 50 MMPIs entering clinical trials have been approved. This work summarizes the reported studies on the structure of MMPs and complexes with ligands and inhibitors, based on which, the authors analyzed the clinical failures of MMPIs in a structural biological manner. Furthermore, MMPs were systematically compared with urokinase, a protease-generating plasmin, which plays similar pathological roles in cancer development; the reasons for the clinical successes of urokinase inhibitors and the clinical failures of MMPIs are discussed.

scholarly journals Understanding the binding of inhibitors of matrix metalloproteinases by molecular docking, quantum mechanical calculations, molecular dynamics simulations, and a MMGBSA/MMBappl study

2015 ◽  
Vol 11 (4) ◽  
pp. 1041-1051 ◽  
Author(s):  
Tanya Singh ◽  
Olayiwola Adedotun Adekoya ◽  
B. Jayaram
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Matrix Metalloproteinases ◽  
Matrix Metalloproteinase ◽  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
Important Class ◽  
Matrix Metalloproteinase Inhibitors ◽  
Metalloproteinase Inhibitors ◽  
Dynamics Simulations

A computationally tractable pathway which helped in understanding the binding of matrix metalloproteinase inhibitors against an important class of MMPs is presented in this article.

Matrix metalloproteinases and matrix metalloproteinase inhibitors in acute lung injury☆

2006 ◽  
Vol 37 (4) ◽  
pp. 422-430 ◽  
Author(s):  
S FLIGIEL ◽  
T STANDIFORD ◽  
H FLIGIEL ◽  
D TASHKIN ◽  
R STRIETER ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Matrix Metalloproteinases ◽  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase Inhibitors ◽  
Metalloproteinase Inhibitors
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