Effects of an oral MMP-9 and -12 inhibitor, AZD1236, on biomarkers in moderate/severe COPD: A randomised controlled trial

Dahl, Ronald; Titlestad, Ingrid Louise; Lindqvist, Ari; Wielders, Pascal; Wray, Heather; Wang, Millie; Samuelsson, Viktoria; Mo, John; Holt, Alison

doi:10.1016/j.pupt.2011.12.011

Cited by 62 publications

(40 citation statements)

References 33 publications

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“…Furthermore, selective MMP-12 inhibitors are available and have been used safely in phase II clinical studies in pulmonary disease [58]. Even so, deeply seated MMP-12 positive macrophages might be difficult to inhibit; and therefore a surrogate marker of efficacy, perhaps based on molecular imaging [59], might be needed as a precursor to any outcome trial.…”

Section: Mmp-12 Promotes Invasion Of Mouse Macrophages In Vitro and Imentioning

confidence: 99%

Metalloproteinases promote plaque rupture and myocardial infarction: A persuasive concept waiting for clinical translation

Newby

2015

Matrix Biology

105

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Atherosclerotic plaque rupture provokes most myocardial infarctions. Matrix metalloproteinases (MMPs) have counteracting roles in intimal thickening, which stabilizes plaques, on the one hand and extracellular matrix destruction that leads to plaque rupture on the other. This review briefly summarizes the key points supporting the involvement of individual MMPs in provoking plaque rupture and discusses the barriers that stand in the way of clinical translation, which can be itemised as follows: structural and functional complexity of the MMP family; lack of adequate preclinical models partly owing to different expression patterns of MMPs and TIMPs in mouse and human macrophages; the need to target individual MMPs selectively; the difficulties in establishing causality in human studies; and the requirement for surrogate markers of efficacy. Overcoming these barriers would open the way to new treatments that could have a major impact on cardiovascular mortality worldwide.

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Section: Mmp-12 Promotes Invasion Of Mouse Macrophages In Vitro and Imentioning

confidence: 99%

Metalloproteinases promote plaque rupture and myocardial infarction: A persuasive concept waiting for clinical translation

Newby

2015

Matrix Biology

105

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“…In contrast, several biologicals that inhibit neutrophil elastase (α1 antiproteinase inhibitors) are in phase 4 post‐marketing confirmatory trials in stable COPD. Divergent results are also seen in this area with trials of SMDs targeting an array of secreted metabolites and intracellular enzymes, such as inhibitors of matrix metalloprotease (MMP)‐9 and of PI3Kδ; receptor antagonists for thromboxane A2 (TXA2), the primary product of COX‐1‐dependent arachidonic acid metabolism; several inhibitors of MAPK and JAK‐STAT pathways (Table ).…”

Section: Biologicals and Smds In Asthma And Copd: Comparison In Theramentioning

confidence: 99%

Comparing biologicals and small molecule drug therapies for chronic respiratory diseases: An EAACI Taskforce on Immunopharmacology position paper

Roth‐Walter

Adcock

Benito-Villalvilla

et al. 2019

Allergy

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Signal transducer and activator of transcription protein; Th17, T helper cells that produce interleukin-17; Th1, T helper 1; Th2, T helper 2; Th9, T helper cells that produce interleukin-9; TNFα, Tumor necrosis factor alpha; TSLP, Thymic stromal lymphopoietin; TBXA2, Tromboxane receptor A2; ULABA, Ultra-long-acting beta-agonists; ULAMA, ultra-long-acting muscarinic agonists; WHO, World Health Organization. † The Task Force of Immunopharmacology (TIPCO) within the Immunology Section of EAACI was established in 2017 to connect scientist and clinicians with the different scientific backgrounds-physicians and basic scientists, pharmacologists, computational biologists-with the task of examining recent breakthroughs on basic mechanisms of immune regulation and review their application in current, upcoming, and paradigm-shifting therapeutic approaches for allergy and clinical immunology-related diseases. The different topics for this first position paper, based on comparison of biologicals and small molecule drug therapeutic approaches, were assigned and drafted by authors' subgroups. They were further discussed, developed, and compiled during a meeting in Salerno (February 24-25, 2018). The position paper draft was thereafter recirculated and critically appraised until the final version was approved by all Task Force Members. AbstractChronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), together with their comorbidities, bear a significant burden on public health. Increased appreciation of molecular networks underlying inflammatory airway disease needs to be translated into new therapies for distinct phenotypes not controlled by current treatment regimens. On the other hand, development of new

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“…This inhibitor was selective for MMP9 and MMP12 with a good safety index. However, more studies are necessary to be carried out for further developments [85]. The structures of some MMP inhibitors are presented in Fig.…”

Section: Mmp9 Inhibitorsmentioning

confidence: 99%

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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Effects of an oral MMP-9 and -12 inhibitor, AZD1236, on biomarkers in moderate/severe COPD: A randomised controlled trial

Cited by 62 publications

References 33 publications

Metalloproteinases promote plaque rupture and myocardial infarction: A persuasive concept waiting for clinical translation

Metalloproteinases promote plaque rupture and myocardial infarction: A persuasive concept waiting for clinical translation

Comparing biologicals and small molecule drug therapies for chronic respiratory diseases: An EAACI Taskforce on Immunopharmacology position paper

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

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