更新于：2024-11-01

MMP14 x MMP8 x MMP2 x MMP1 x MMP9

更新于：2024-11-01

基本信息

关联

项与 MMP14 x MMP8 x MMP2 x MMP1 x MMP9 相关的药物

Rebimastat

瑞马司他

靶点

MMP1 x MMP14 x MMP2 x MMP8 x MMP9

作用机制

MMP1抑制剂 [+4]

在研机构-

原研机构

Celltech Oy

在研适应症-

非在研适应症

乳腺癌 [+3]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

项与 MMP14 x MMP8 x MMP2 x MMP1 x MMP9 相关的临床试验

NCT00040755 / Completed临床2期IIT

Randomized Phase II Trial of BMS-275291 (NSC 713763, IND 62573) in Hormone Refractory Prostate Cancer

BMS-275291 may stop the growth of prostate cancer by stopping blood flow to the tumor and by blocking the enzymes necessary for tumor cell growth. Randomized phase II trial to study the effectiveness of BMS-275291 in treating patients who have prostate cancer that has not responded to hormone therapy

开始日期2002-05-01

申办/合作机构

National Cancer Institute

NCT00039104 / Completed临床2期IIT

A Phase II, Open-Label, Randomized Trial of Zoledronic Acid (Zometa™) and BMS-275291 (NSC#713763) in Patients With Hormone Refractory Prostate Cancer

Phase II trial to study the effectiveness of combining zoledronate with BMS-275291 in treating patients who have prostate cancer that has not responded to previous hormone therapy. Zoledronate may prevent bone loss and stop the growth of tumor cells in bone. BMS-275291 may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Combining zoledronate with BMS-275291 may kill more tumor cells.

开始日期2002-04-01

申办/合作机构

National Cancer Institute

100 项与 MMP14 x MMP8 x MMP2 x MMP1 x MMP9 相关的临床结果

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100 项与 MMP14 x MMP8 x MMP2 x MMP1 x MMP9 相关的转化医学

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0 项与 MMP14 x MMP8 x MMP2 x MMP1 x MMP9 相关的专利（医药）

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项与 MMP14 x MMP8 x MMP2 x MMP1 x MMP9 相关的文献（医药）

2023-12-01·CARTILAGE

Is the Synovium the First Responder to Posttraumatic Knee Joint Stress? The Molecular Pathogenesis of Traumatic Cartilage Degeneration

Article

作者: Elphingstone, Joseph ; Kwapisz, Adam ; Herman, Katarzyna ; Synder, Marek ; Szemraj, Janusz ; Piwnik, Marcin ; Momaya, Amit ; Grzegorzewski, Andrzej

Objective The aim of this study was to evaluate if a similar catabolic and inflammatory gene pattern exists between the synovium, hyaline cartilage, and blood of patients with the knee joint tissues and if one precedes the other. Design A total of fifty-eight patients (34 females and 24 males) with a mean age of 44.7 years (range, 18-75) underwent elective knee arthroscopy due to previously diagnosed pathology. Full blood samples were collected preoperatively from synovium and cartilage samples intraoperatively. Real time PCR with spectrophotometric analysis was performed. Following genes taking part in ECM (extracellular matrix) remodeling were selected for analysis: MMP-1, MMP-2, MMP-8, MMP-9, MMP-13, MMP-14, ADAMTS-4 (Agg1) and ADAMTS-5 (Agg2) proteases, TIMP-1, and TIMP-2 – their inhibitors - and IL-1 and TNF-α cytokines. Results Analysis revealed a strong and significant correlation between gene expression in synovial and systemic blood cells (p <0.05 for all studied genes) with ADAMTS-4, ADAMTS-5, IL-1, TNF-α and TIMP-2 expression most positively correlated with an R>0.8 for each. An analysis between chondrocytes and systemic blood gene expression shown no significant correlation for all genes. Bivariate correlation of International Cartilage Repair Society grading and genes expression revealed significant associations with synovial MMP-1, MMP-2, MMP-8, MMP-9, IL-1, TNF-α and TIMP-2. Conclusion We suggest that the synovial tissue is the first responder for knee joint stress factors in correlation with the response of blood cells. The chondrocyte’s genetic response must be further investigated to elucidate the genetic program of synovial joints, as an organ, during OA development and progression.

2022-11-01·International Immunopharmacology

Atorvastatin attenuates NS1 (Non-structural protein-1) of dengue type-2 serotype-induced expressions of matrix metalloproteinases in HL-60 cells, differentiated to neutrophils: Implications for the immunopathogenesis of dengue viral disease

Article

作者: Sankari, T ; Sunilkumar, Anupama ; Vidhyapriya, Pitchavel ; Kumar, Ashwani ; Ganesh, Khashpatika ; Niranjan, Rituraj ; Muthukumaravel, Subramanian ; Manoj, H ; Murugasamy, Vyshali

BACKGROUNDThe dengue is a vector borne viral infection in humans. Bite of mosquito infected with a dengue virus transmits the disease. The neutrophils support more to the innate immune response by switching to infected tissues and triggering immunomodulatory mechanisms including the release of proteases and host defence peptides.METHODSCell viability by MTT and trypan blue dye exclusion assay, bright field microscopy for assessment of cell morphology, cytokines measurements by ELISA, estimation of protein by Bradford assay were done. Assessments of matrix metalloproteinase genes mRNA expressions were done using real-time PCR.RESULTSIn the present study, we have for the first time unveiled that, NS1 antigen of dengue type-2 serotype, induce and stimulate the neutrophils cells to express high levels of matrix metalloproteases. NS1 exposure of HL-60 cells differentiated to neutrophils affected cell morphology and in 24 h of exposure. We have demonstrated that, the NS1 antigen has induced MMP-2, MMP-14 and MMP-9 expressions in neutrophils in a 24hrs exposure time. NS1 exposure has also further upregulated MMP-1, MMP-13, and MMP-8 expressions in neutrophils in a 24hrs exposure time. Notably, treatment with atorvastatin concentrations downregulated the expression profile of the all matrix metalloprotease significantly. Importantly, NS1 antigen has significantly increased the IL-6, IL-13 release by the HL,60 cells which was reversed by atorvastatin. On the other hand, NS1 exposure enhanced the mRNA expressions of VEGF-A and VEGF-D which was reversed by atorvastatin. However, we found that, NS1 exposure reduced the mRNA expressions profile of VEGF-C, which was reversed by atorvastatin.CONCLUSIONIn conclusion, we report that, neutrophils associated matrix metalloprotease are involved in the pathogenesis of dengue viral disease. VEGF growth factors may also be released by the neutrophils which may subsequently participate in the endothelial dysfunctions leading to dengue shock syndrome.

2021-12-01·The FEBS Journal3区 · 生物学

Multifunctional intracellular matrix metalloproteinases: implications in disease

3区 · 生物学

Review

作者: Bassiouni, Wesam ; Schulz, Richard ; Ali, Mohammad A. M.

Matrix metalloproteinases (MMPs) are zinc‐dependent endopeptidases that were first discovered as proteases, which target and cleave extracellular proteins. During the past 20 years, however, intracellular roles of MMPs were uncovered and research on this new aspect of their biology expanded. MMP‐2 is the first of this protease family to be reported to play a crucial intracellular role where it cleaves several sarcomeric proteins inside cardiac myocytes during oxidative stress‐induced injury. Beyond MMP‐2, currently at least eleven other MMPs are known to function intracellularly including MMP‐1, MMP‐3, MMP‐7, MMP‐8, MMP‐9, MMP‐10, MMP‐11, MMP‐12, MMP‐14, MMP‐23 and MMP‐26. These intracellular MMPs are localized to different compartments inside the cell including the cytosol, sarcomere, mitochondria, and the nucleus. Intracellular MMPs contribute to the pathogenesis of various diseases. Cardiovascular renal disorders, inflammation, and malignancy are some examples. They also exert antiviral and bactericidal effects. Interestingly, MMPs can act intracellularly through both protease‐dependent and protease‐independent mechanisms. In this review, we will highlight the intracellular mechanisms of MMPs activation, their numerous subcellular locales, substrates, and roles in different pathological conditions. We will also discuss the future direction of MMP research and the necessity to exploit the knowledge of their intracellular targets and actions for the design of targeted inhibitors.