更新于：2024-11-01

NF-κB x ADAM17

更新于：2024-11-01

基本信息

关联

项与 NF-κB x ADAM17 相关的药物

ORTD-1

靶点

ADAM17 x NF-κB

作用机制

ADAM17 modulators [+1]

在研机构-

原研机构

Oryn Therapeutics LLC

在研适应症-

非在研适应症

新型冠状病毒感染 [+2]

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 NF-κB x ADAM17 相关的临床试验

NCT04708236 / Withdrawn临床1/2期

A Blinded, Controlled, Escalating Dose Study of ORTD-1 for Treatment of Hospitalized Patients With SARS-CoV-2 (COVID-19) Related Pneumonia.

Evaluate the safety and effect of ORTD-1 on COVID-19 related pneumonia.

开始日期2021-04-01

申办/合作机构

Oryn Therapeutics LLC

NCT04286789 / Completed临床1期

A Randomized, Double-blind, Parallel, Vehicle Controlled, Repeat Dose Comparative Phase 1b Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ORTD-1 in Rheumatoid Arthritis Patients With Mild Disease Managed With DMARDs

This is a randomized, vehicle controlled, double-blind, repeat dose comparative study in patients with rheumatoid arthritis (RA) under management with DMARDs and with persistent disease activity. The goal of this study is to evaluate the safety, tolerability and pharmacokinetics of 6 weekly repeat doses of ORTD-1.

开始日期2021-03-22

申办/合作机构

Oryn Therapeutics LLC

100 项与 NF-κB x ADAM17 相关的临床结果

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100 项与 NF-κB x ADAM17 相关的转化医学

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0 项与 NF-κB x ADAM17 相关的专利（医药）

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118

项与 NF-κB x ADAM17 相关的文献（医药）

2025-01-01·Current Neuropharmacology

Role of Metalloproteinases in Diabetes-associated Mild Cognitive Impairment

Review

作者: Prather, Jonathan F. ; Nair, Sreejayan ; Pradhanang, Suyasha ; Pereira, Vitoria Mattos

:Diabetes has been linked to an increased risk of mild cognitive impairment (MCI), a condition characterized by a subtle cognitive decline that may precede the development of dementia. The underlying mechanisms connecting diabetes and MCI involve complex interactions between metabolic dysregulation, inflammation, and neurodegeneration. A critical mechanism implicated in diabetes and MCI is the activation of inflammatory pathways. Chronic low-grade inflammation, as observed in diabetes, can lead to the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and interferon-gamma (IFNγ), each of which can exacerbate neuroinflammation and contribute to cognitive decline. A crucial enzyme involved in regulating inflammation is ADAM17, a disintegrin, and metalloproteinase, which can cleave and release TNF-α from its membrane-bound precursor and cause it to become activated. These processes, in turn, activate additional inflammation-related pathways, such as AKT, NF-κB, NLP3, MAPK, and JAK-STAT pathways. Recent research has provided novel insights into the role of ADAM17 in diabetes and neurodegenerative diseases. ADAM17 is upregulated in both diabetes and Alzheimer's disease, suggesting a shared mechanism and implicating inflammation as a possible contributor to much broader forms of pathology and pointing to a possible link between inflammation and the emergence of MCI. This review provides an overview of the different roles of ADAM17 in diabetes-associated mild cognitive impairment diseases. It identifies mechanistic connections through which ADAM17 and associated pathways may influence the emergence of mild cognitive impairment.

2024-12-01·Cellular Signalling

Fangchinoline inhibits metastasis and reduces inflammation-induced epithelial-mesenchymal transition by targeting the FOXM1-ADAM17 axis in hepatocellular carcinoma

Article

作者: Abd El-Aty, A M ; Wang, Mengyuan ; Zhang, Xinbin ; Ji, Jiansong ; Fang, Shiji ; Chen, Minjiang ; Wang, Jianbo ; Zhang, Yeyu ; Zhang, Huajun ; Rajamanickam, Vinothkumar ; Zhao, Zhongwei ; Linnebacher, Michael ; Zheng, Liyun

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Efforts have been focused on developing new anti-HCC agents and understanding their pharmacology. However, few agents have been able to effectively combat tumor growth and invasiveness due to the rapid progression of HCC. In this study, we discovered that fangchinoline (FAN), a bisbenzylisoquinoline alkaloid derived from Stephania tetrandra S. Moore, effectively inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of HCC cells. FAN treatment also led to the suppression of IL6 and IL1β release, as well as the expression of inflammation-related proteins such as COX-2 and iNOS, and the activation of the NF-κB pathway, thereby reducing inflammation-related EMT. Additionally, FAN directly bound to forkhead box protein M1 (FOXM1), resulting in decreased levels of FOXM1 proteins and disruption of the FOXM1-ADAM17 axis. Our in vivo findings confirmed that FAN effectively hindered the growth and lung metastasis of HCCLM3-xenograft tumors. Importantly, the upregulation of FOXM1 in HCC tissue suggested that targeting FOXM1 inhibition with FAN or its inhibitors could be a promising therapeutic approach for HCC. Overall, this study elucidated the anti-tumor effects and potential pharmacological mechanisms of FAN, and proposed that targeting FOXM1 inhibition may be an effective therapeutic strategy for HCC with potential clinical applications.

2024-11-01·European Journal of Pharmacology

Synthetic and non-synthetic inhibition of ADAM10 and ADAM17 reduces inflammation and oxidative stress in LPS-induced acute kidney injury in male and female mice

Article

作者: Huner Yigit, Merve ; Yigit, Ertugrul ; Yilmaz Kutlu, Eda ; Topal Suzan, Zehra ; Karabulut, Soner ; Atak, Mehtap

Acute kidney injury (AKI) is a severe medical condition that can lead to illness and death. A disintegrin and metalloprotease (ADAM) protein family is a potential treatment target for AKI due to its involvement in inflammation, growth, and differentiation. While ADAM10 and ADAM17 have been identified as significant contributors to inflammation, it is unclear whether they play a critical role in AKI. In this study, we induced AKI in male and female mice using lipopolysaccharide, a bacterial endotoxin that causes inflammation and oxidative stress. The role of kaempferol, which is found in many natural products and known to have antioxidant and anti-inflammatory activity in many pre-clinical studies, was investigated through ADAM10/17 enzymes in AKI. We also investigated the efficacy of a selective synthetic inhibitor named GW280264X for ADAM10/17 inhibition in AKI. Blood urea nitrogen and creatinine levels were measured in serum, while tumor necrosis factor-α, vascular adhesion molecule, interleukin (IL)-1β, glucose regulatory protein-78, IL-10, nuclear factor κ-B, thiobarbituric acid reactive substances, total thiol, ADAM10, and ADAM17 levels were measured in kidney tissue. We also evaluated kidney tissue histologically using hematoxylin and eosin, periodic acid-schiff, and caspase-3 staining. This research demonstrates that GW280264X and kaempferol reduces inflammation and oxidative stress, as evidenced by biochemical and histopathological results in AKI through ADAM10/17 inhibition. These findings suggest that inhibiting ADAM10/17 may be a promising therapeutic approach for treating acute kidney injury.