Sofalcone, a gastroprotective drug, covalently binds to KEAP1 to activate Nrf2 resulting in anti-colitic activity

Kim, Wooseong; Lee, Hanju; Kim, Soojin; Joo, Sanghyun; Jeong, Seongkeun; Yoo, Jin‐Wook; Jung, Yunjin

doi:10.1016/j.ejphar.2019.172722

Cited by 23 publications

(18 citation statements)

References 35 publications

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“…Honaucin A forms a covalent bond with the sulfhydryl groups on KEAP1, resulting in the activation of NRF2 [85]. Many food-based NRF2 activators have been shown to work in multiple organs such as liver [86], lung [87], kidney [88], brain [89] and gastrointestinal tract [90]. Most of these NRF2 activating compounds are phenol, polyphenol, or triterpenoid.…”

Section: Natural Compoundsmentioning

confidence: 99%

Potential Applications of NRF2 Modulators in Cancer Therapy

et al. 2020

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The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation. Thus, a better understanding of the mechanisms that control NRF2 functions and the most appropriate context of its activation is a prerequisite for the development of effective therapeutic strategies based on NRF2 modulation. In line of principle, the controlled activation of NRF2 might reduce the risk of cancer initiation and development in normal cells by scavenging reactive-oxygen species (ROS) and by preventing genomic instability through decreased DNA damage. In contrast however, already transformed cells with constitutive or prolonged activation of NRF2 signaling might represent a major clinical hurdle and exhibit an aggressive phenotype characterized by therapy resistance and unfavorable prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, describing the mechanisms of its activation and potential therapeutic strategies based on the use of context-specific modulation of NRF2.

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Section: Natural Compoundsmentioning

confidence: 99%

Potential Applications of NRF2 Modulators in Cancer Therapy

et al. 2020

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“…Nevertheless, the wide range of biological activities associated with chalcones has elicited significant interest among medicinal and synthetic chemists from academic and industrial laboratories, resulting in the continuous development of new applications around the chalcone core. , Metochalcone and sofalcone are two clinically approved medicinal chalcones. While metochalcone is an anti-cholerectic drug, sofalcone is used as an oral medication in Japan to treat ulcers . Chalcones have also been found to be valuable intermediates in the preparation of pharmaceuticals, agrochemicals, and advanced materials.…”

Section: Introductionmentioning

confidence: 99%

“…While metochalcone is an anti-cholerectic drug, sofalcone is used as an oral medication in Japan to treat ulcers. 32 Chalcones have also been found to be valuable intermediates in the preparation of pharmaceuticals, agrochemicals, and advanced materials.…”

Section: ■ Introductionmentioning

confidence: 99%

Orchestrating a β-Hydride Elimination Pathway in Palladium(II)-Catalyzed Arylation/Alkenylation of Cyclopropanols Using Organoboron Reagents

2022

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The scope of chemoselective β-hydride elimination in the context of arylation/alkenylation of homoenolates from cyclopropanol precursors using organoboronic reagents as transmetalation coupling partners was examined. The reaction optimization paradigm revealed a simple ligand-free Pd(II) catalytic system to be most efficient under open air conditions. The preparative scope, which was investigated with 48 examples, supported the applicability of this reaction to a wide range of substrates tolerating a variety of functional groups while delivering β-substituted enone and dienone derivatives in 62−95% yields.

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“…Sofalcone also has mucosal protective properties, inhibits growth of H. pylori and has been used to treat gastritis and gastric ulcers in Japan for decades. These protective properties stem from activation of the cytoprotective and anti-inflammatory nuclear factor-erythroid 2 (NF-E2) p45related factor 2 (Nrf2)-heme oxygenase (HO)-1 pathway [68]. Sofalcone disrupts binding of the Kelch-like ECHassociated protein 1 (KEAP1), a cytosolic repressor of Nrf2 activation [68,69] and increases VEGF via an Nrf2-HO-1 dependent pathway in gastric epithelial cells [70].…”

Section: Sofalconementioning

confidence: 99%

“…These protective properties stem from activation of the cytoprotective and anti-inflammatory nuclear factor-erythroid 2 (NF-E2) p45related factor 2 (Nrf2)-heme oxygenase (HO)-1 pathway [68]. Sofalcone disrupts binding of the Kelch-like ECHassociated protein 1 (KEAP1), a cytosolic repressor of Nrf2 activation [68,69] and increases VEGF via an Nrf2-HO-1 dependent pathway in gastric epithelial cells [70]. KEAP1 is a tumor and metastasis suppressor gene [71].…”

Section: Sofalconementioning

confidence: 99%

Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline

Melrose¹,

Smith²

2022

Front. Biosci. (Elite Ed)

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The aim of this review is to highlight the beneficial attributes of flavonoids, a diverse family of widely-distributed polyphenolic phytochemicals that have beneficial cell and tissue protective properties. Phytochemicals are widely distributed in plants, herbs and shrubs used in traditional complimentary medical formulations for centuries. The bioactive components that convey beneficial medicinal effects in these complex herbal preparations are now being identified using network pharmacology and molecular docking procedures that identify their molecular targets. Flavonoids have anti-oxidant, anti-inflammatory, antiviral, antibacterial and anti-cancer properties that have inspired the development of potent multifunctional derivatised flavonoids of improved efficacy. The antiviral properties of flavonoids and the emergence of the severe acute respiratory syndrome (SARS-CoV-2) pandemic has resulted in a resurgence of interest in phytochemicals in the search for efficacious compounds that can prevent viral infection or replication, with many promising plant compounds identified. Promising semi-synthetic flavonoid derivatives have also been developed that inhibit multiple pathological neurodegenerative processes; these offer considerable promise in the treatment of diseases of cognitive decline. Clinical trials are currently being undertaken to evaluate the efficacy of dietary supplements rich in flavonoids for the treatment of virally-mediated diseases. Such trials are expected to identify flavonoids with cell and tissue protective properties that can be harnessed in biomedical applications that may serve as supportive adjunctive procedures to conventional anti-viral drug therapies against diseases such as COVID-19.

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Sofalcone, a gastroprotective drug, covalently binds to KEAP1 to activate Nrf2 resulting in anti-colitic activity

Cited by 23 publications

References 35 publications

Potential Applications of NRF2 Modulators in Cancer Therapy

Potential Applications of NRF2 Modulators in Cancer Therapy

Orchestrating a β-Hydride Elimination Pathway in Palladium(II)-Catalyzed Arylation/Alkenylation of Cyclopropanols Using Organoboron Reagents

Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline

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