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Last update 08 May 2025

ADAM17 x NF-κB

Last update 08 May 2025

Basic Info

Related Targets

ADAM17NF-κB

Drugs associated with ADAM17 x NF-κB

ORTD-1

Target

ADAM17 x NF-κB

Mechanism

ADAM17 modulators [+1]

Active Org.-

Originator Org.

Oryn Therapeutics LLC

Active Indication-

Inactive Indication

COVID-19 [+2]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with ADAM17 x NF-κB

NCT04708236

/ WithdrawnPhase 1/2

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.

Start Date01 Apr 2021

Sponsor / Collaborator

Oryn Therapeutics LLC

NCT04286789

/ CompletedPhase 1

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.

Start Date22 Mar 2021

Sponsor / Collaborator

Oryn Therapeutics LLC

100 Clinical Results associated with ADAM17 x NF-κB

100 Translational Medicine associated with ADAM17 x NF-κB

0 Patents (Medical) associated with ADAM17 x NF-κB

150

Literatures (Medical) associated with ADAM17 x NF-κB

01 Feb 2025·Journal of Medical Virology

Tumor Necrosis Factor‐Alpha Inhibits the Replication of Patient‐Derived Archetype BK Polyomavirus While Activating Rearranged Strains

Article

Author: Fliser, Danilo ; Toews, Lina Kathrin ; Lauterbach, Marcel A. ; Sternjakob, Anna ; Möller, Lars ; Stöckle, Michael ; Smola, Sigrun ; Thuringer, Lucia ; Klinz, Jonas ; Rahmann, Sven ; Walter, Jörn ; Gasparoni, Gilles ; Lohse, Stefan ; Schmit, David ; Lauterbach‐Rivière, Lise ; Janssen, Martin ; Laue, Michael ; Gläser, Lars ; Kattler‐Lackes, Kathrin ; Schüssler, Jessica ; Feld, Pascal

ABSTRACTTo date, no drugs are approved for BK polyomavirus (BKPyV) reactivation, a major cause of nephropathy after kidney transplantation. Recently, tumor necrosis factor‐α (TNF‐α) blockade has been proposed as a promising therapy, however, the effect of TNF‐α on the clinically most common archetype (ww) BKPyV remained unclear. Assays in primary renal proximal tubule epithelial cells (RPTEC) allowed efficient replication only of BKPyV strains with rearranged (rr) non‐coding control regions (NCCR), which may develop at later disease stages, but not of ww‐BKPyV. Here, we optimized culture conditions allowing robust replication of patient‐derived ww‐BKPyV, while efficiently preserving their ww‐NCCR. TNF‐α promoted rr‐BKPyV replication, while the TH1 cytokine IFN‐γ suppressed it, also in the presence of TNF‐α. Surprisingly, TNF‐α alone was sufficient to suppress all ww‐BKPyV strains tested. Comprehensive analysis using siRNAs, and chimeric or mutated BKPyV‐strains revealed that the response to TNF‐α depends on the NCCR type, and that the NF‐κB p65 pathway but not the conserved NF‐κB binding site is essential for the TNF‐α‐induced enhancement of rr‐BKPyV replication. Our data suggest that in immunosuppressed patients with archetype‐dominated infections, TNF‐α blockade could interfere with natural TNF‐α‐mediated anti‐BKPyviral control, and this could be detrimental when IFN‐γ‐driven TH1 responses are impaired. Ongoing inflammation, however, could lead to the selection of rearrangements responding to NCCR‐activating pathways downstream of NF‐κB p65 signaling, that may overcome the initial TNF‐α‐mediated suppression. Our findings also highlight the importance of using clinically relevant BKPyV isolates for drug testing and discovery, for which this new assay paves the way.

01 Jan 2025·Current Neuropharmacology

Role of Metalloproteinases in Diabetes-associated Mild Cognitive Impairment

Review

Author: 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.

01 Jan 2025·BioFactors

Curcumin attenuates ulcerative colitis via regulation of Sphingosine kinases 1/NF‐κB signaling pathway

Article

Author: Zhang, Hao ; Lin, Jiumao ; Zhang, Xiuli ; Chen, Hui ; Wu, Cheng ; Chen, Yangyi ; Wang, Qingshui ; Wang, Jingting ; Lin, Yao

AbstractCurcumin, a compound from Curcuma longa L., has significant anti‐inflammatory properties. However, the mechanisms underlying its anti‐inflammatory activity in dextran sodium sulfate (DSS)‐induced ulcerative colitis (UC) remain inadequately understood. This study aimed to further elucidate the molecular mechanisms of curcumin DSS‐induced UC mice. Our data showed that curcumin alleviated DSS‐induced colitis by reducing intestinal damage and inflammation, increasing goblet cells in colon tissues. Enzyme‐linked immunosorbent assay revealed that curcumin reduced the expression of inflammatory cytokines (tumor necrosis factor‐alpha, interleukin‐1β, and interleukin‐8) in serum and myeloperoxidase in colon tissues. A comprehensive analysis integrating network pharmacology and RNA sequencing (RNA‐seq) revealed significant enrichment of the nuclear factor kappa B (NF‐κB) signaling pathways. Notably, RNA‐seq analysis demonstrated that curcumin significantly downregulated the mRNA expression of sphingosine kinase 1 (SphK1). Furthermore, molecular docking analysis showed that curcumin can bind to SphK1 and NF‐κB. Additionally, curcumin was found to inhibit the activation of the SphK1/NF‐κB signaling pathway in DSS‐induced UC colon tissue. This study addresses pharmacologic and mechanistic perspectives of curcumin that ameliorates DSS‐induced UC and inflammatory response.

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