Matrix metalloproteinase 9 (MMP9) in wound healing of diabetic foot ulcer: Molecular target and structure-based drug design

Hariono, Maywan; Yuliani, Sri Hartati; Istyastono, Enade Perdana; Riswanto, Florentinus Dika Octa; Adhipandito, Christophorus Fideluno

doi:10.1016/j.wndm.2018.05.003

Cited by 51 publications

(46 citation statements)

References 91 publications

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“…To the best of our knowledge, there are only three publications reporting compounds inhibiting PEX9 including pyrimidine-arylamide [101,103] and steroid [102] scaffolds. This is in contrast with studies targeting MMP9 with the catalytic domain as the protein target covering diverse scaffolds such as pyridinone, pyridithiol, biaryl ether sulfonamide hydroxamate, aryl sulfone, pyrimidine, aromatic carboxylic acid and flavonoid which have been reviewed in our previous published article [13]. The distinction of structure amongst the hemopexin domains is promising a better target for selective inhibition rather than the catalytic domains, which share highly conserved amino acid residues in their binding sites.…”

Section: Discussion and Current Researchmentioning

confidence: 95%

“…The binding assay study revealed the K d of four hit compounds (11, 12, 13 and 14) in low micromolar inhibitions (0.6 μM, 0.8 μM, 0.9 μM and 0.8 μM, respectively). The structure of those four compounds (11)(12)(13)(14) are presented in Fig. 7.…”

Section: Computational Drug Modelling Targeting Hemopexin Of Mmp9mentioning

confidence: 99%

“…This 7 shows solvent exposure surrounds difluoromethoxyphenol which decreases the free energy of Fig. 7 The four hit compounds active against PEX9 selected from NCI database (11)(12)(13)(14) [98], the derivatives of 7 (15 [98] binding. In addition, the planar quinazolinone was said to improve the ligand-binding efficiency as well as the longer flexible propyl chain.…”

Section: Computational Drug Modelling Targeting Hemopexin Of Mmp9mentioning

confidence: 99%

“…Structurally, MMPs are zinc-dependent endopeptidases classified as protease enzymes [9]. The main function of these enzymes is to degrade the ECM, which is involved in various physiological processes such as wound healing, inflammation, angiogenesis, vasculogenesis and metastasis [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Matrix metalloproteinase9 as the protein target in anti-breast cancer drug discovery: an approach by targeting hemopexin domain

et al. 2019

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Background: The discovery and development of anticancer still remain a challenge especially regarding the problem of cancer cell selectivity. Matrix metalloproteinase (MMP) was broadly studied as one of the protein targets to stop cancer angiogenesis as well as its cell migration. Main text: The MMP degrades extracellular matrix (ECM) such as collagen and gelatin which are important to control the cell migration from one to other sites. In cancer, this cell migration is regarded with metastasis, which is essential for the formation of new blood vessels called angiogenesis. The most common target in MMP, i.e. the catalytic site, is currently reported as being the non-selective target for inhibitor compounds that inhibit all MMPs but is associated with adverse side effects. Hemopexin, especially in MMP9 (PEX9) was found to be different from other domains in the MMP family which could potentially be the next target for anticancer due to the availability of its crystal structure in the Protein Data Bank (PDB). Conclusion: The PEX9 crystal structure was resolved as a homodimer connected by a hydrophobic area between two blades along the β-propeller which its structure and function for computational drug modelling can be studied.

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Section: Discussion and Current Researchmentioning

confidence: 95%

Section: Computational Drug Modelling Targeting Hemopexin Of Mmp9mentioning

confidence: 99%

Section: Computational Drug Modelling Targeting Hemopexin Of Mmp9mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Matrix metalloproteinase9 as the protein target in anti-breast cancer drug discovery: an approach by targeting hemopexin domain

et al. 2019

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“…Whether this might be explained by biases in highly expressed genes in the RNAseq workflow, or other technical considerations, MMP9 expression needs to be further examined. Nonetheless, upregulation of MMPs in individuals with type II diabetes impedes effective wound healing 37.…”

mentioning

confidence: 99%

Transcriptomic analysis of adhesive capsulitis of the shoulder

Kamal

McGee

Eng

et al. 2020

Journal Orthopaedic Research

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Adhesive capsulitis (AC) is a disabling condition of the shoulder joint affecting 2 to 5% of the general population. Our understanding of the molecular mechanisms is limited. The present study aimed to determine potential biomarkers of AC through transcriptomic analysis. This multi‐centre study investigated patients undergoing arthroscopic capsulotomy surgery for resistant AC compared to those undergoing arthroscopic stabilization surgery for glenohumeral instability (control). Tissue samples were harvested from the anterior capsule during surgery. Total RNA was extracted and RNA‐sequencing‐based transcriptomics were performed. A number of genes deemed differentially expressed in RNA‐sequencing analysis were validated using real‐time reverse transcription polymerase chain reaction (RT‐PCR). Baseline characteristics of the AC group (n = 22) were; mean age 52.7 years (SD: 10.2), 73% female, and Oxford Shoulder Score 19.6 (SD: 8.0), compared with the control group (n = 26), average age 23.9 years (SD: 5.2), 15% female, and Oxford Shoulder Score 39.0 (SD: 7.4). Transcriptomic analysis with false discovery rate correction and log2 fold change cut‐off of ±1.5 revealed 545 differentially expressed genes in AC relative to control. Bioinformatic analyses were carried out to identify biological processes and pathways enriched in this dataset. Real‐time RT‐PCR using two different normalization processes confirmed increased expression of matrix metallopeptidase 13 (MMP13) and platelet‐derived growth factor subunit B (PDGFB), in patients with AC, while tumor necrosis factor α (TNFA) expression was reduced. These findings provide a comprehensive assessment of transcriptional changes associated with AC that give insights into the aetiology of the disease and provides a resource for molecular targets to better diagnose and treat this condition.

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State‐of‐the‐Art and Future Challenges of Smart Wound Dressings for Diabetic Foot Ulcer Treatment

Szunerits,

Boukherroub

2024

Advanced NanoBiomed Research

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The slow healing process of diabetic wound due to persisting infections in wound bed, owing to hyperglycemia, makes the search for efficient treatments pending. While it is complicated to increase the wound closure rate in diabetic‐related wounds due to the complex pathology, the treatment of such wound with hydrogels is seen as a promising approach and pursued over the years. However, where is this research currently standing in terms of clinical translation of these different multifunctional and stimuli‐responsive hydrogel bandages to accelerate diabetic foot ulcer healing and help to improve the life of the patients and the future of diabetic wound management? This perspective article will review some of the most important advancements in the field and will conclude with some perspectives, considered as relevant in the clinical context.

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Matrix metalloproteinase 9 (MMP9) in wound healing of diabetic foot ulcer: Molecular target and structure-based drug design

Cited by 51 publications

References 91 publications

Matrix metalloproteinase9 as the protein target in anti-breast cancer drug discovery: an approach by targeting hemopexin domain

Matrix metalloproteinase9 as the protein target in anti-breast cancer drug discovery: an approach by targeting hemopexin domain

Transcriptomic analysis of adhesive capsulitis of the shoulder

State‐of‐the‐Art and Future Challenges of Smart Wound Dressings for Diabetic Foot Ulcer Treatment

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