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Last update 08 May 2025

NKRF

Last update 08 May 2025

Basic Info

Synonyms

ITBA4, NF-kappa-B-repressing factor, NF-kappaB repressing factor

+ [6]

Introduction

Enhances the ATPase activity of DHX15 by acting like a brace that tethers mobile sections of DHX15 together, stabilizing a functional conformation with high RNA affinity of DHX15 (PubMed:12381793). Involved in the constitutive silencing of the interferon beta promoter, independently of the virus-induced signals, and in the inhibition of the basal and cytokine-induced iNOS promoter activity (PubMed:12381793). Also involved in the regulation of IL-8 transcription (PubMed:12381793). May also act as a DNA-binding transcription regulator: interacts with a specific negative regulatory element (NRE) 5'-AATTCCTCTGA-3' to mediate transcriptional repression of certain NK-kappa-B responsive genes (PubMed:10562553).

Drugs associated with NKRF

Uroacitides

Target

NKRF

Mechanism

NF-kappa-B-repressing factor inhibitors

Active Org.

Hefei Everlife Pharmaceutical Co., Ltd.

Originator Org.

Hefei Lifeon Pharmaceutical Co., Ltd.

Active Indication

Breast Cancer [+2]

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

China

First Approval Date23 Jul 2004

Triolex

Target

ERK x NKRF

Mechanism

ERK inhibitors [+1]

Active Org.

BioVie, Inc. [+1]

Originator Org.

Harbor Diversified, Inc. [+1]

Active Indication

Alzheimer Disease [+7]

Inactive Indication

Amyotrophic Lateral Sclerosis [+18]

Drug Highest PhasePhase 3

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

INO-2002

Target

NKRF

Mechanism

NF-kappa-B-repressing factor inhibitors

Active Org.-

Originator Org.

Inotek Pharmaceuticals Corp.

Active Indication-

Inactive Indication

Colitis, Ulcerative [+1]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with NKRF

NCT06847191

/ RecruitingPhase 2

A Double-blind, Randomized Study to Evaluate the Efficacy and Safety of Bezisterim (NE3107) in Adults With Long COVID

Long COVID is a condition where debilitating symptoms can persist for months after a COVID-19 infection. This study aims to evaluate the effects of NE3107 on several neurological symptoms reported in people with Long COVID including difficulty concentrating or remembering things ("brain fog") and fatigue.
Researchers will compare NE3107 to a placebo (a look-alike substance that contains no drug) to see if NE3107 works to treat neurocognitive and fatigue symptoms of long COVID.
Participants will:
* Take NE3107 or a placebo twice daily for 84 days
* Visit the clinic 5 times for checkups and tests and have a follow up phone call

Start Date01 Apr 2025

Sponsor / Collaborator

BioVie, Inc.

NCT06757010

/ RecruitingPhase 2

A Double-Blind, Randomized, Placebo-controlled, Study of NE3107 in Subjects With Early Parkinson's Disease

The goal of this clinical trial is to learn if bezisterim can treat movement symptoms of Parkinson's disease in patients that are 45 to 80 years old, in generally good physical and mental health, and are nearing the need for treatment to relieve their symptoms but have not yet been prescribed any form of levodopa or drug with similar activity. The main questions it aims to answer are:
* Will bezisterim decrease movement symptoms of Parkinson's disease?
* What medical problems do participants have when taking bezisterim?
Researchers will compare the effects of bezisterim treatment to placebo (a look-alike substance that contains no drug) to see if bezisterim works to treat movement symptoms of Parkinson's disease.
Participants will
* have a physical examination that includes an electrocardiogram
* take drug or placebo twice daily for four months
* visit a clinical site or receive an at home visit seven times over the course of five months

Start Date26 Mar 2025

Sponsor / Collaborator

BioVie, Inc.

NCT05970575

/ RecruitingPhase 2IIT

Open Label Phase IIa Study Evaluating the Safety and Efficacy of NE3107 in Improving Sleep and Fatigue in Subjects With Traumatic Brain Injury

This study seeks to measure changes in cognition through verbal and visual test procedures and changes in biomarkers of Traumatic Brain Injury and inflammatory and metabolic parameters.

Start Date21 Dec 2023

Sponsor / Collaborator

BioVie, Inc.

100 Clinical Results associated with NKRF

100 Translational Medicine associated with NKRF

0 Patents (Medical) associated with NKRF

451

Literatures (Medical) associated with NKRF

01 May 2025·Aquatic Toxicology

Molecular basis for the effects of SSRIs in non-target aquatic invertebrates: A case study with Mytilus galloprovincialis early larvae

Article

Author: Miglioli, Angelica ; Balbi, Teresa ; Dumollard, Rémi ; Canesi, Laura ; Risso, Beatrice

Selective Serotonin Reuptake Inhibitors (SSRIs) are among the most prescribed antidepressants, whose increasing consumption results in a continuous discharge into aquatic compartments, where they are detected at ng-µg/L levels. Whilst designed to modulate endogenous levels of circulating Serotonin (5-HT) in humans by selectively interfering with serotonin reuptake transporters (SERTs), SSRIs have been shown to induce a variety of adverse effects in non-target species, including aquatic invertebrates. In bivalve molluscs, adult exposure to environmental concentrations of SSRIs results in tissue bioaccumulation and induces different biomarker responses. However, the effects were not related to the mechanisms of action of SSRIs, due to poor knowledge of their direct molecular targets, SERT in particular. Much less information is available in embryo-larval stages. In this work, the effects of different SSRIs (Fluoxetine, Citalopram, Sertraline, 1-100 µg/L) were compared in the model of Mytilus galloprovincialis embryo-larval development. SSRIs showed small or no effects on normal larval development at 48 h post fertilization (hpf). The possible direct or indirect molecular targets of SSRIs were thus investigated in mussel larvae. Two conserved SERT sequences, SERT1-like and SERT2-like, were identified in M. galloprovincialis genome: their developmental expression showed increased transcription only from 44 and 20 hpf, respectively. A much higher and earlier expression (from 12 hpf) was observed for TPH (Tryptophan Hydroxylase), the rate limiting enzyme in 5-HT synthesis. Double in situ Hybridization Chain Reaction (HCR) showed partial colocalisation of TPH with SERT1-like and SERT2-like transcripts in 48 hpf larvae. At this stage, SSRIs induced a small but significant decrease in the number of TPH-positive cells. Finally, 19 Nose Resistance to Fluoxetine (nrf) sequences were identified, that were highly expressed across all early stages (0-48 hpf). At 48 hpf, nrf expression was associated with the digestive system. The results represent the first data on the establishment of the serotonergic system in mussel early larvae, representing the molecular basis for understanding the effects of SSRIs and their mechanisms of action in model non-target marine invertebrates.

01 Apr 2025·Biofabrication

Oxytocin‐loaded hydrogel promotes cartilage regeneration and regulates microenvironment

Article

Author: Wang, Binghao ; Zheng, Shengnai ; Xie, Jiaming ; Jiang, Bo ; Cao, Zhicheng ; Sui, Jisheng ; Li, Jiayi ; Wang, Yufeng ; Zhu, Kun ; Zhao, Xiao ; Yin, Chongchong ; Yao, Qingqiang ; Wang, Tianming

AbstractOsteoarthritis is a common orthopedic condition, and traditional treatment methods often fail to regenerate cartilage effectively. Oxytocin (OXT) is a neuropeptide that plays a crucial role in the skeletal system. Hyaluronic acid (HAMA) hydrogel has emerged as a key carrier for cartilage repair due to its excellent biocompatibility and biodegradability. Combining OXT with HAMA hydrogel and implanting it at the site of cartilage defects can effectively promote cartilage regeneration. Cartilage damage often results in an altered microenvironment, characterized by macrophage polarization and high levels of reactive oxygen species (ROS). Oxidative stress can stimulate macrophages to produce more pro-inflammatory factors. OXT can inhibit the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β by interacting with the STAT3/NF-κB signaling pathway, as well as the PI3K/Akt and mitogen-activated protein kinase pathways, thereby inducing the polarization of macrophages from the M1 phenotype to the M2 phenotype and alleviating the inflammatory response. OXT can also enhance the expression of NRF and HO-1, which helps eliminate ROS and suppress the expression of pro-inflammatory factors. Regulating the microenvironment of cartilage damage is beneficial for cartilage protection and repair. OXT activates the CFOS/AP-1 and STAT1/JAK2 pathways, which together act on MMP2 and MMP9 to alleviate cartilage degeneration. The STAT1/JAK2 pathway can further increase the expression of Col2, thereby protecting chondrocytes. Additionally, OXT can directly boost the protein levels of SOX9 and COMP, promoting chondrocyte proliferation and cartilage protection, ultimately achieving the therapeutic goal for arthritis. This study explores the potential of HAMA hydrogel as a delivery system for OXT and analyzes their impact on cartilage regeneration and anti-inflammatory properties. This research provides a novel strategy for the treatment of cartilage injuries.

01 Mar 2025·Pigment Cell & Melanoma Research

Piceatannol—Can It Be Used to Treat Hyperpigmentation of the Skin?

Review

Author: Rajan, Ravi Kumar

ABSTRACTOver the years, the cosmetic industry has shifted its focus from synthtic to natural compounds. This change is driven not only by the safety profile of natural ingredients but also by increased consumer awareness about the products they use. As a result, many natural skincare products have been launched in recent years. Hyperpigmentation disorders, such as melasma, age spots (solar lentigines), post‐inflammatory hyperpigmentation, freckles, and acanthosis nigricans, are significant concerns. These conditions not only pose pathological issues but also affect individuals' self‐esteem. Consequently, treating hyperpigmentation by reducing melanogenesis has become a key area of interest in cosmetology. Among various natural compounds, piceatannol (PCT) shows great potential in treating hyperpigmentation. The primary mechanism previously explored is the inhibition of the tyrosinase enzyme, which is one of the most researched strategies for combating melanogenesis. Additionally, PCT has been shown to downregulate MITF expression, a key gene responsible for the transcription of various melanogenic proteins and enzymes. However, beyond these two mechanisms, little is known about how PCT may inhibit melanogenesis. In this review, we aim to bridge that gap. We will explore and speculate on the possible upstream signaling pathways to MITF, such as Nrf, FOXO3a, CREB, MAPK signaling, etc., where PCT could potentially act to inhibit melanogenesis. This review will not only pave the way for future research related to PCT and hyperpigmentation but also highlight pathways that could be targeted for developing cosmetics and treatments for hyperpigmentation disorders.

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