Chemical and Environmental Toxicology

Signosis’ NRF2/ARE luciferase reporter cell line provides a robust and sensitive system for evaluating chemical-induced oxidative stress and identifying potential environmental toxicants that impact cellular redox balance. The NRF2 pathway is a primary cellular defense mechanism activated in response to reactive oxygen species (ROS), xenobiotics, and electrophilic compounds—many of which are found in industrial chemicals, pesticides, air pollutants, and heavy metals.

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This reporter system enables real-time, quantifiable measurement of ARE-driven gene transcription, making it ideally suited for chemical safety testing, regulatory toxicology, and screening of potential endocrine-disrupting or genotoxic compounds. Such applications include:

• Screening for environmental toxins, air pollutants, or industrial chemicals that activate or inhibit NRF2 signaling.

• Investigating the potential health effects of long-term exposure to chemicals or stressors that may affect NRF2 pathway regulation.

• Studying the molecular basis of oxidative stress-related diseases like Alzheimer's, Parkinson’s, or cardiovascular disease.

• Identifying biomarkers of environmental exposure and oxidative stress.​

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Common inducers and inhibitors that can be used with this model:

• Sulforaphane, tert-butylhydroquinone (tBHQ), curcumin, or Resveratrol to activate NRF2 signaling

• ML385, brusatol, or sunitinib to inhibit NRF2 activity.

• Inflammatory cytokines, NF-κB modulators, or metal chelators for interaction between pathways

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Signosis provides NRF2/ARE luciferase reporter cell lines for high-throughput environmental screening and regulatory toxicology studies. This model enables accurate identification of redox-active chemicals, contributing to safer product development and more informed risk management practices.

Disease Modeling and Redox Biology

Signosis’ NRF2/ARE luciferase reporter cell line offers a powerful platform for studying the role of oxidative stress and antioxidant signaling in disease contexts, including neurodegeneration, cardiovascular disease, diabetes, and cancer. Dysregulation of the NRF2 pathway has been implicated in both protective and pathogenic roles depending on the disease stage and tissue context, making it a critical focus for redox-related biomedical research.

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This system allows researchers to explore how NRF2 activation influences cellular defense, survival, and metabolic adaptation under stress conditions. It is especially relevant for modeling chronic oxidative stress associated with aging, inflammation, and metabolic disorders. Applications include:

• Investigating the role of NRF2 in diseases characterized by oxidative stress, such as Parkinson’s, Alzheimer’s, atherosclerosis, and diabetic complications.

• Modeling chronic or excessive NRF2 activation in how it contributes to cancer progression, chemoresistance, or immune evasion.

• Evaluating antioxidant therapies or NRF2-targeted treatments for neuroprotective, cardioprotective, or anti-inflammatory effects.

• Studying redox regulation of genes involved in detoxification, inflammation, autophagy, and cell survival.

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Common inducers and inhibitors that can be used with this model:

• Sulforaphane, dimethyl fumarate (DMF), Resveratrol, or bardoxolone methyl to activate NRF2 signaling

• ML385, brusatol, KEAP1 overexpression or siRNA to inhibit NRF2 activity.

• TNF-α, LPS, PI3K/AKT modulators, or ROS inducers like H₂O₂ as modulators for cross-talk studies

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Signosis provides NRF2/ARE luciferase reporter cell lines for mechanistic studies into the role of oxidative stress in chronic disease, as well as therapeutic screening for redox-targeted interventions. Its high sensitivity and adaptability make it a key tool for researchers studying the complex interplay between stress response pathways and disease progression.

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Drug Screening and Compound Discovery

Signosis’ NRF2/ARE luciferase reporter cell line provides a high-throughput platform for identifying and characterizing compounds that modulate oxidative stress responses through the NRF2 signaling pathway. Given NRF2’s central role in cellular defense, inflammation, and metabolism, this model is particularly valuable for early-stage drug discovery targeting oxidative damage, metabolic disorders, chronic inflammation, and cancer.

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This system enables real-time quantification of NRF2 activity in response to chemical compounds, allowing researchers to rapidly assess both on-target efficacy and potential off-target effects. It is suitable for screening natural products, small molecules, or biologics for their ability to either promote or inhibit NRF2 signaling. Applications include:

• High-throughput screening of libraries for compounds that activate NRF2 to enhance cellular protection and resilience.

• Identifying NRF2 inhibitors for therapeutic use in cancers where constitutive NRF2 activation drives chemoresistance.

• Profiling redox-related pharmacodynamics across drug candidates to assess safety, efficacy, and stress response.

• Evaluating drug-induced oxidative stress and determining whether NRF2 signaling is involved in adaptive or toxic responses.

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Common inducers and inhibitors that can be used with this model:

• Sulforaphane, tBHQ, DMF, Resveratrol, or bardoxolone methyl to activate NRF2 signaling

• ML385, brusatol, KEAP1 overexpression to inhibit NRF2 activity.

• Electrophilic stressors, PI3K/AKT modulators, or ROS inducers like H₂O₂ to simulate drug-induced stress

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Signosis offers the NRF2/ARE luciferase reporter cell line as a robust and reproducible tool for redox-targeted drug screening. This system supports compound prioritization, structure-activity relationship (SAR) studies, and early-stage toxicity assessment within pharmaceutical R&D pipelines.

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Inflammation and Immune Modulation

Signosis’ NRF2/ARE luciferase reporter cell line serves as a powerful tool for investigating the role of NRF2 in modulating immune responses and inflammation. NRF2, a key regulator of the cellular antioxidant response, has been shown to suppress proinflammatory cytokine production by inhibiting NF-κB signaling pathways. This makes the reporter system particularly valuable for studying the impact of NRF2 activation on immune cell behavior and inflammatory processes.

This system enables real-time, quantitative measurement of NRF2 activity in response to various stimuli, allowing researchers to assess how NRF2 influences immune cell activation, cytokine production, and the resolution of inflammation. Applications include:

• Studying NRF2’s regulatory role in inflammation-driven oxidative stress and cytokine signaling

• Evaluating anti-inflammatory drug candidates that modulate NRF2 activity

• Exploring cross-talk between NRF2 and inflammatory pathways such as NF-κB or JAK/STAT

• Assessing the redox status of inflamed or stressed cells in response to exogenous stimuli

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Common inducers and inhibitors that can be used with this model:

• Sulforaphane, tBHQ, Resveratrol, or bardoxolone methyl to activate NRF2 signaling

• ML385, brusatol, or KEAP1 overexpression to inhibit NRF2 activity

• LPS, TNF-α, NF-κB inhibitors, or IL-1β as modulators for cross-talk studies

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Signosis offers NRF2/ARE luciferase reporter cell lines for inflammation-focused research in non-immune models, enabling high-throughput assessment of redox-inflammation interactions in disease and drug discovery.