A review of MMP-2 structures and binding mode analysis of its inhibitors to strategize structure-based drug design

Sanyal, Shankha; Amin, Sk. Abdul; Banerjee, Priyanka; Gayen, Shovanlal; Jha, Tarun

doi:10.1016/j.bmc.2022.117044

Cited by 9 publications

(6 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…187−189 Apart from this, an in-silico method is also used to design advanced medicine specific to the inflammatory activity and help to improve the therapeutics' role in TB disease. 190 These advancements have the potential to revolutionize the field of drug delivery and enhance the efficacy and safety of therapeutic TB interventions. In the future, MMP inhibitors will make a robust platform for therapeutics that selectively respond to MMP expression and regulation by improving immunopathology in TB, and this will fetch the next-generation drug delivery system in anti-TB therapy.…”

Section: Challengesmentioning

confidence: 99%

Breaking the Cycle: Matrix Metalloproteinase Inhibitors as an Alternative Approach in Managing Tuberculosis Pathogenesis and Progression

Jhilta,

Jadhav,

Singh

et al. 2024

ACS Infect. Dis.

View full text Add to dashboard Cite

Mycobacterium tuberculosis (Mtb) has long posed a significant challenge to global public health, resulting in approximately 1.6 million deaths annually. Pulmonary tuberculosis (TB) instigated by Mtb is characterized by extensive lung tissue damage, leading to lesions and dissemination within the tissue matrix. Matrix metalloproteinases (MMPs) exhibit endopeptidase activity, contributing to inflammatory tissue damage and, consequently, morbidity and mortality in TB patients. MMP activities in TB are intricately regulated by various components, including cytokines, chemokines, cell receptors, and growth factors, through intracellular signaling pathways. Primarily, Mtb-infected macrophages induce MMP expression, disrupting the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs), thereby impairing extracellular matrix (ECM) deposition in the lungs. Recent research underscores the significance of immunomodulatory factors in MMP secretion and granuloma formation during Mtb pathogenesis. Several studies have investigated both the activation and inhibition of MMPs using endogenous MMP inhibitors (i.e., TIMPs) and synthetic inhibitors. However, despite their promising pharmacological potential, few MMP inhibitors have been explored for TB treatment as host-directed therapy. Scientists are exploring novel strategies to enhance TB therapeutic regimens by suppressing MMP activity to mitigate Mtbassociated matrix destruction and reduce TB induced lung inflammation. These strategies include the use of MMP inhibitor molecules alone or in combination with anti-TB drugs. Additionally, there is growing interest in developing novel formulations containing MMP inhibitors or MMP-responsive drug delivery systems to suppress MMPs and release drugs at specific target sites. This review summarizes MMPs' expression and regulation in TB, their role in immune response, and the potential of MMP inhibitors as effective therapeutic targets to alleviate TB immunopathology.

show abstract

Section: Challengesmentioning

confidence: 99%

Breaking the Cycle: Matrix Metalloproteinase Inhibitors as an Alternative Approach in Managing Tuberculosis Pathogenesis and Progression

Jhilta,

Jadhav,

Singh

et al. 2024

ACS Infect. Dis.

View full text Add to dashboard Cite

show abstract

“…Therefore, the regulation and inhibition of MMPs is an important therapeutic approach to combat these pathologies, and MMP inhibitors can be used as antitumor agents. However, to date, more than 50 different MMP inhibitors have been found to be ineffective in clinical trials [20,21]. Nevertheless, further research in this direction with the aim of developing new selective MMP inhibitors in the fight against cancer remains relevant.…”

Section: The Role Of Various Mpps In Cancer Developmentmentioning

confidence: 99%

Antitumor Properties of Matrikines of Different Origins: Prospects and Problems of Their Application

Popov,

Kozlovskaya,

Rutckova

et al. 2023

IJMS

View full text Add to dashboard Cite

Matrikines (MKs) can be a rich source of functional nutrition components and additional therapy, thereby contributing to human health care and reducing the risk of developing serious diseases, including cancer. Currently, functionally active MKs as products of enzymatic transformation by matrix metalloproteinases (MMPs) are used for various biomedical purposes. Due to the absence of toxic side effects, low species specificity, relatively small size, and presence of various targets at the cell membranes, MKs often exhibit antitumor properties and, therefore, are promising agents for antitumor combination therapy. This review summarizes and analyzes the current data on the antitumor activity of MKs of different origins, discusses the problems and prospects for their therapeutic use, and evaluates the experimental results of studying the antitumor properties of MKs from different echinoderm species generated with the help of a complex of proteolytic enzymes from red king crab Paralithodes camtschatica. Special attention is paid to the analysis of possible mechanisms of the antitumor action of various functionally active MKs, products of the enzymatic activity of various MMPs, and the existing problems for their use in antitumor therapy.

show abstract

“…Given that budding tumor cells produce MMPs to invade the stroma and promote tumor progression, the inhibition of MMP activity could potentially prevent the degradation of the ECM and reduce tumor budding-associated invasion and metastasis. To that end, several MMP inhibitors have been developed, with some undergoing preclinical and clinical testing for their potential efficacy in CRC treatment [ 182 , 183 ].…”

Section: Tumor Budding and Its Influence On The Tumor Stroma In Crcmentioning

confidence: 99%

Cellular and Molecular Mechanisms of the Tumor Stroma in Colorectal Cancer: Insights into Disease Progression and Therapeutic Targets

Shakhpazyan,

Mikhaleva,

Bedzhanyan

et al. 2023

Biomedicines

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a major health burden worldwide and is the third most common type of cancer. The early detection and diagnosis of CRC is critical to improve patient outcomes. This review explores the intricate interplay between the tumor microenvironment, stromal interactions, and the progression and metastasis of colorectal cancer. The review begins by assessing the gut microbiome’s influence on CRC development, emphasizing its association with gut-associated lymphoid tissue (GALT). The role of the Wnt signaling pathway in CRC tumor stroma is scrutinized, elucidating its impact on disease progression. Tumor budding, its effect on tumor stroma, and the implications for patient prognosis are investigated. The review also identifies conserved oncogenic signatures (COS) within CRC stroma and explores their potential as therapeutic targets. Lastly, the seed and soil hypothesis is employed to contextualize metastasis, accentuating the significance of both tumor cells and the surrounding stroma in metastatic propensity. This review highlights the intricate interdependence between CRC cells and their microenvironment, providing valuable insights into prospective therapeutic approaches targeting tumor–stroma interactions.

show abstract

A review of MMP-2 structures and binding mode analysis of its inhibitors to strategize structure-based drug design

Cited by 9 publications

References 118 publications

Breaking the Cycle: Matrix Metalloproteinase Inhibitors as an Alternative Approach in Managing Tuberculosis Pathogenesis and Progression

Breaking the Cycle: Matrix Metalloproteinase Inhibitors as an Alternative Approach in Managing Tuberculosis Pathogenesis and Progression

Antitumor Properties of Matrikines of Different Origins: Prospects and Problems of Their Application

Cellular and Molecular Mechanisms of the Tumor Stroma in Colorectal Cancer: Insights into Disease Progression and Therapeutic Targets

Contact Info

Product

Resources

About