NEDD9 inhibitors(neural precursor cell expressed, developmentally down-regulated 9 inhibitors), NUF2 inhibitors(NUF2 component of NDC80 kinetochore complex inhibitors), Nrf2 stimulants(Nuclear factor erythroid 2-related factor 2 stimulants)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesNervous System Diseases+ [8]

Active Indication

Common Variable ImmunodeficiencyInterstitial lung disease due to systemic diseaseCarpal Tunnel Syndrome+ [10]

Inactive Indication

Meniscus disorderPost Acute COVID 19 Syndrome

Originator Organization

Mayo Clinic

Active Organization

University of Wisconsin-Madison

Mayo ClinicHvidovre University Hospital

+ [4]

Inactive Organization

University of Kentucky

License Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC15H10O6

InChIKeyXHEFDIBZLJXQHF-UHFFFAOYSA-N

CAS Registry528-48-3

Clinical Trials associated with Fisetin

NCT07025226

/ RecruitingEarly Phase 1IIT

MC230715 Pilot Study of the Mechanistic Feedback From CNS Tumors With Latent Residual Disease to Guide Individualized Therapies

This early phase I trial tests the safety, side effects and how well medication combinations of dasatinib, quercetin, fisetin and temozolomide work in treating patients with glioma for which the patient has received treatment in the past (previously treated) and for tumor cells that remain after attempts to treat the tumor have been made (residual disease). Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply, which may help keep tumor cells from growing. Quercetin and fisetin are compounds found in plants. They have antioxidant and anti-inflammatory properties and help remove senescent cells, older or damaged cells that have stopped dividing but don't die off as they should and build up in tissues over time. Senescent cells may cause inflammation or damage to nearby healthy cells. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells and slow down or stop tumor growth. Giving medication combinations of dasatinib, quercetin, fisetin and temozolomide may be safe, tolerable and/or effective in treating patients with previously treated glioma with residual disease.

Start Date12 Aug 2025

Sponsor / Collaborator

Mayo Clinic

NCT05505747

/ WithdrawnPhase 2/3IIT

Enhancing Recovery Through a Combined Mechanobiologic Intervention Following Meniscus Repair

Arthroscopic meniscal procedures are the most commonly performed orthopaedic procedure in the U.S. affecting 15% of Americans ages 10-65 years. Meniscus injury is also known to increase the risk of posttraumatic osteoarthritis (PTOA). The current randomized clinical trial will test a novel intervention after meniscal repair that combines an oral senolytic fisetin and real-time biofeedback program to restore joint loading and subsequent return to activity.

Start Date01 Jul 2025

Sponsor / Collaborator

University of Kentucky

ChiCTR2500100733

/ Not yet recruitingEarly Phase 1IIT

Evaluation of Urolithin A and Fisetin on Improving Sleep and Aging Biomarkers

Start Date01 May 2025

Sponsor / Collaborator-

100 Clinical Results associated with Fisetin

100 Translational Medicine associated with Fisetin

100 Patents (Medical) associated with Fisetin

2,873

Literatures (Medical) associated with Fisetin

01 Feb 2026·COMPUTATIONAL BIOLOGY AND CHEMISTRY

Computational and experimental investigation of Kaempferol and Quercetin as potential inhibitors of MMP1 in oral cancer

Article

Author: Kumar, Sivakumar Prasanth ; Jain, Nayan K ; Patel, Prabhudas S ; Thakore, Vaidehi P ; Uppalapati, Sai Swetha ; Mandoli, Amit

Oral Cancer (OC) remains the most frequently reported malignancy characterized by low survival-rate, attributing to the lack of effective therapeutic-targets. Activities of several proteases, particularly matrix metalloproteinase (MMPs), induce epidermal hyperplasia increasing susceptibility to tumorogenesis. Their dual-nature in disease, wide-substrate specificity, and compensatory machinery makes them challenging to target. MMPs inhibitors have faced consequential challenges in clinical-applications. Hence, present study aimed to identify natural inhibitors of MMPs to aid preventive measures against OC carcinogenesis and therapeutics. Current study analyzed gene-expression of MMP1, MMP3, and MMP10 in tissues of head and neck cancer and normal, suggesting MMP1 as potential target. Virtual screening was performed to identify potential natural inhibitor for MMP1 target. Molecular Dynamic simulations (MDS) supported the binding abilities of the prioritized compounds, and ADMET analysis showed promising pharmacokinetic and pharmacodynamics properties. Computational findings were validated using in-vitro analysis and MMPs gene expression was evaluated after treatment in Cal27 and NOE cell lines. The results showed significant overexpression of MMPs in tumor samples and were strongly associated with clinico-pathological characteristics. Virtual screening identified L-epicatechin, 3-O-Methylquercetin, Fisetin, Quercetin, and Kaempferol as potential MMP1 inhibitors with high binding-affinity. Further, Kaempferol and Quercetin showing stability, conformation, and intermolecular interactions through MDS were prioritized for in-vitro validation. Kaempferol and Quercetin exhibited anti-proliferative and anti-migratory effects on Cal27 cells in time- and dose-dependent manners. Impaired gene-expression of MMPs after the treatment suggested potential of these compounds in preventing tumor invasion and metastasis and highlighted them as therapeutic-agents for the treatment-strategies in OC.

01 Jan 2026·COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY

Fisetin modulates fluoride induced osteochondral toxicity in zebrafish larvae

Article

Author: Perumal, Ekambaram ; Sreedharan, Theeksha ; Ottappilakkil, Harsheema ; Yesudas, Grace Helena

Excessive fluoride (F^-) exposure, particularly during early development, poses a significant risk to skeletal integrity by disrupting bone homeostasis through oxidative stress and altered mineralization. While F^- induced oxidative stress is well documented, studies investigating the role of natural antioxidants in mitigating F^- induced osteochondral toxicity remain limited. Hence, the present study investigated the osteomodulatory effect of fisetin (Fis) against F^- toxicity in zebrafish larvae. Fis (15 μM) was exposed to zebrafish larvae at 3 days post fertilization (dpf) for 24 h, followed by 72 h exposure to 25 ppm sodium fluoride (NaF). F^- accumulation, oxidant (ROS, LPO, NO, PCC) and antioxidant (SOD, CAT, GSH) levels, cartilage (alcian blue staining), skeletal (alizarin red staining, hydroxyproline content, ALP activity) markers, and expression of osteochondral genes (sox9b, runx2b, ocn, osx, col1a1, alp, rankl, and opg) were assessed in control and treated larvae. F^- exposure significantly elevated oxidative stress, disrupted craniofacial cartilage morphology, and induced premature ossification, alongside altered expression of osteogenic and resorptive markers. Remarkably, Fis pretreatment effectively reduced F^- accumulation, restored redox homeostasis, preserved cartilage architecture, and normalized mineral deposition. Gene expression analysis further confirmed that Fis modulated key regulators of osteogenesis, chondrogenesis, and bone resorption, underscoring its osteoprotective role. Collectively, these findings demonstrate that Fis confers protection against F^- induced osteochondral toxicity by attenuating oxidative stress, supporting bone matrix development, and regulating genes essential for bone homeostasis.

01 Dec 2025·Stress biology

Transcriptional modification and the accumulation of flavonoid in the leaves of Cissus rotundifolia Lam. in respond to drought stress

Author: Gituru, Robert Wahiti ; Hou, Yujun ; Gichuki, Duncan Kiragu ; Xin, Haiping ; Zhou, Huimin ; Wang, Qingfeng ; Li, Qingyun

Abstract:

Cissus rotundifolia Lam. is an evergreen climber that mainly distributed in the tropical savannas of eastern Africa with excellent drought resistance. While the mechanism underlying drought stress response in C. rotundifolia remains unknown. In this study, we investigated the transcriptomics and flavonoid metabolomics responses of C. rotundifolia leaves under different drought conditions. We identified a total of 2401 differentially expressed genes (DEGs) in drought-treated leaves. The continuously increasing DEGs were significantly enriched in pathways related to phenylpropanoid biosynthesis, flavonoid biosynthesis, and galactose metabolism. The total flavonoids content were also found increased significantly during drought treatment in the leaves of C. rotundifolia. A total of 57 distinct flavonoids were identified using UPLC-MS/MS. Among them, nine out of ten differentially accumulated metabolites (DAMs) displayed notable accumulation profiles under drought conditions. These DAMs included two flavanols [(-)-Catechin gallate and (-)-gallocatechin gallate], two flavonols (myricetin and astragalin), four flavones (orientin, cynaroside, isoorientin, and vitexin), and one flavanone (naringenin-7-glucoside), indicating their pivotal roles in drought response. Additionally, a DEG with continuously high-expression, annotated flavone synthase (FLS) synthesises, and synthetizing myricetin under drought stress was tightly related to additional genes belonging to ABA-signaling genes, stomata movement genes, transcription factors, and protein kinases, these genes were contained Top 10 hub-genes of network constructed all DEGs. The results reflect the significance of FLS and potentially regulatory genes under drought conditions. These findings suggest that flavonoids play a pivotal role in the drought stress response of C. rotundifolia, advancing our understanding of flavonoids accumulation and the transcriptional regulation involved in this process.

News (Medical) associated with Fisetin

14 Apr 2025

·www.businesswire.com

BeFisetin® Announced the Global No.1 All-Natural Fisetin With SA-GRAS Status

NEW YORK--(BUSINESS WIRE)--Bonerge Lifescience, a trusted innovator in longevity ingredients, proudly announces a historic milestone: on April 2, 2025, its premium fisetin ingredient, BeFisetin®, has achieved Self-affirmed Generally Recognized as Safe (SA-GRAS) status in the United States. This landmark accomplishment positions Bonerge as the first company globally to secure GRAS certification for fisetin powder, setting a new global benchmark for safety and reliability in the next-generation anti-aging market. BeFisetin: Establishing the Gold Standard to Address Chaos in the Fisetin Market The current fisetin market is plagued by alarming quality inconsistencies. While vague claims of "Fisetin 98% HPLC" dominate as the mainstream specification, actual fisetin content in these products ranges only between 75%-85%, with significant impurities concealed under this ambiguous standard. For plant extracts derived from non-edible sources, the removal of harmful components is critical. Fisetin, extracted from inedible Anacardiaceae plants, contains large amounts of toxic lacquer, waxes, and wood debris. Eliminating these impurities is essential to producing safe, high-quality fisetin. Yet, the absence of clear, stringent quality standards has made it impossible to verify purity, allowing low-quality products to flood the market. Many suppliers exploit rudimentary testing methods to falsely label products as "98% HPLC," misleading consumers and perpetuating a cycle where inferior products overshadow genuine quality. This chaos forces brands to settle for subpar fisetin, stifling innovation in premium formulations. Establishing a gold standard for fisetin quality has been Bonerge’s mission from the start. Recognizing the challenges—extensive R&D, industry-first breakthroughs, and short-term financial sacrifices—we named our product BeFisetin as a constant reminder: "To be or not to be" hinges on our commitment to redefine excellence in fisetin. BeFisetin is not just a product—it’s a pledge to restore integrity and drive progress in the fisetin industry. What Defines the Gold Standard for Fisetin? Safety First : SA-GRAS certification ensures systemic safety evaluation, a critical gateway for market entry. Transparent Quality Metrics : BeFisetin guarantees 98% HPLC purity , 98% HPLC content , 99% total active ingredients , and <1% impurities , setting unmatched benchmarks for consistency and quality. Ongoing Clinical Validation : Bonerge has completed the first double-blind, controlled clinical trial on BeFisetin’s efficacy in skin health, with results under analysis and pending publication. A second large-scale trial on sleep and immune health, approved by ethics committees in March, is now underway. BeFisetin: The 1st All-Natural Fisetin to be Granted SA-GRAS BeFisetin® is the first all-natural fisetin to attain SA-GRAS certification. For all dietary supplement ingredients, SA-GRAS represents a critical milestone, but its significance is unparalleled in advancing fisetin as a premium raw material. This certification sets the gold standard for the industry, requiring adherence to rigorous criteria: well-defined quality specifications, scientifically validated testing protocols, GMP-compliant manufacturing environments, and comprehensive safety assessments—all of which elevate fisetin from an underregulated botanical to a clinically trusted ingredient. By establishing these benchmarks, SA-GRAS not only ensures consumer safety but also paves the way for innovation in longevity-focused formulations. “Beyond regulatory compliance, this accomplishment reflects our foundational commitment to scientific excellence and consumer safety—principles that drive every stage of our ingredient innovation,” stated Gloria, Product Manager of Bonerge. “SA-GRAS BeFisetin® provides brands with a scientifically validated ingredient that meets international regulatory requirements, enabling them to develop innovative products with assurance.” A Vision for Trusted Longevity Foundation The GRAS certification of BeFisetin® marks the beginning of Bonerge’s mission to redefine aging. By prioritizing rigorous science and consumer safety, Bonerge aims to foster transparency in the anti-aging market, and we are committed to providing scientifically grounded solutions that empower individuals to age healthily. As global interest in senotherapeutics grows, BeFisetin® stands at the forefront, offering brands a trusted, scalable ingredient to meet the rising demand for effective and safe longevity products.

Drug Approval

09 Jan 2025

·www.businesswire.com

Bonerge Announces the New 108 Person Clinical Trial: Exploring Skin and Organ Anti-Aging Innovations

NEW YORK--( BUSINESS WIRE )--Bonerge announced the initiation of its clinical trial, focusing on Fisetin, Urolithin A, and Ergothioneine. Involving 108 participants, this trial aims to evaluate their combined effects on skin health and organ rejuvenation when taking orally, providing more reliable options for the market. Senolytics Research: Advancing the Science of Anti-Aging In recent years, Senolytics research has advanced rapidly, with institutions like the Mayo Clinic and Wake Forest University at the forefront. Despite fruitful research, identifying optimal applications to translate Senolytics into market solutions remains crucial. In October 2024, the Mayo Clinic published groundbreaking findings in Nature Aging, identifying 67 plasma proteins, with IL-23R emerging as a promising anti-aging biomarker 1 . The study explored various promising Senolytics, including Fisetin, demonstrating a positive response in reducing senescence-related proteins and indicating potential for organ rejuvenation via senescent cell clearance 2 . The concept of organ rejuvenation offering deeper insights into its systemic effects and guiding anti-aging strategies. Senolytics show strong potential for organ rejuvenation applications and promise broader future prospects. Bonerge’s Clinical Trial: Exploring Skin as the Key to Rejuvenation The skin, the largest organ of the human body, is the most visible indicator of aging and a key target for anti-aging. Bonerge has launched a clinical trial focused on skin anti-aging, involving 108 participants. The trial evaluates skin anti-aging effects by assessing factors like skin heme, skin inflammation, transepidermal water loss, wrinkles, skin elasticity, skin firmness, melanin levels, and skin tone. Spanning 56 days, it aligns with two skin regeneration cycles, providing a detailed analysis of these key skin health indicators. Three ingredients tested in the trail: Fisetin: Among natural ingredients, fisetin has the strongest activity in clearing senescent cells. Its core mechanism promotes apoptosis of senescent cells and reduces SASP (Senescence-Associated Secretory Phenotype) secretion, alleviating chronic inflammation and combating inflammaging 3 , contributing to organ rejuvenation. Urolithin A: A rising star in nutritional supplements, Urolithin A has shown significant anti-photoaging effects. Photoaging, primarily caused by UVA (ultraviolet A) radiation, accelerates skin aging. Urolithin A helps protect skin by reducing the senescent phenotype of skin fibroblasts triggered by UVA, lowering intracellular ROS (reactive oxygen species), and activating antioxidant enzymes. These actions collectively support skin health and combat the harmful effects of photoaging 4 . Ergothioneine : Currently recognized as the only antioxidant that targets mitochondria, it reduces oxidative damage within mitochondria, supporting energy production and potentially preventing cellular aging 5 . Key Focus: Exploring Individual Ingredients and Combined Synergies In this clinical trial, while examining the skin anti-aging effects of individual ingredients, the combination of the three ingredients have also been tested to explore the synergistic effects on skin health and anti-aging. Path Ahead: Trial Progress and Future Expectations The clinical trial is progressing as planned and is expected to conclude in March 2025. Bonerge is hopeful that this study will provide valuable evidence for the anti-aging market, paving the way for the application of Senolytics in skin health and broader anti-aging treatments. References [1] Chase M. Carver, et al. IL-23R is a senescence-linked circulating and tissue biomarker of aging. Nature Aging, Dec 2024. [2] Researchers discover an aging and inflammation biomarker - Mayo Clinic News Network [3] Matthew J. et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine 36 (2018). [4] Wenjie Liu , et al. Urolithin A protects human dermal fibroblasts from UVA-induced photoaging through NRF2 activation and mitophagy. J Photochem Photobiol B. 2022 Jul. [5] Brown, Lisa, et al. L-Ergothioneine and Its Protective Role in Cellular Health. Journal of Clinical Nutrition, vol 56.

Clinical Study

31 Dec 2024

·www.businesswire.com

BeFisetin® is Gaining the First Fisetin Ingredient SA-GRAS Certification

NEW YORK--( BUSINESS WIRE )--In 2024, Bonerge's premium fisetin branded ingredient, BeFisetin®, initiated the SA-GRAS (Self-Affirmed Generally Recognized As Safe) certification process, with completion expected in February 2025. This certification underscores Bonerge's unwavering commitment to product safety, quality control and serves as a key milestone in its expansion into the global fisetin market. Fisetin: The Anti-aging Potential of Natural Polyphenols Fisetin is a natural polyphenol widely present in various fruits and vegetables such as strawberries, apples, and persimmons. In recent years, the scientific community's enthusiasm for exploring fisetin has been continuously rising. Numerous research findings have revealed that fisetin has unique biological properties in reducing inflammatory factors, strengthening cell health, and delaying aging [1-3], and its related applications have also attracted extensive and in-depth attention. Biochemical studies have shown that fisetin can exert its effects through multiple mechanisms. It can effectively reduce senescent cells in the brain, skin, and various organs, regulate inflammatory factors, and scavenge free radicals [4]. This makes fisetin an attractive dietary supplement, showing broad application prospects in healthy aging and long-term health management. BeFisetin®: Marketing Strategy and Innovation As a company dedicated to the development and research of high-quality ingredients, Bonerge recognizes the growing global demand for safe and effective dietary supplements. It is Bonerge’s principle to leverage cutting-edge science to transform advanced research into practical health solutions. Bonerge is continuously improving the purity and bioavailability of BeFisetin®, while integrating sustainable production practice, demonstrating a strong commitment to environmental responsibility. Focusing on the great potential of fisetin, Bonerge has engaged in in-depth strategic collaborations with multiple research institutions and universities to strengthen the scientific validation and credibility of BeFisetin®, continuously enhancing its trust and reputation through rigorous scientific verification. This ensures consumers have access to transparent, reliable health solutions. SA-GRAS Certification: An Extended Standard in Safety and Trust SA-GRAS certification, a critical extension of the FDA's GRAS framework, allows companies to confirm the safety of their products through rigorous self-assessment. This process involves establishing stringent product standards, conducting comprehensive toxicity and safety evaluations, and systematically assessing raw materials, manufacturing processes, and product stability. Companies need to work with independent professional organizations to prepare detailed safety assessment reports, which are reviewed by an expert panel. The rigorous certification process drives Bonerge to further optimize its product quality systems and elevated BeFisetin®'s competitiveness in the global market. For Bonerge, SA-GRAS certification is not merely a regulatory milestone but a testament to its relentless pursuit of product excellence and its commitment to consumer safety. Looking Ahead: Responsibility and Opportunity The expansion of aging population is a global challenge, driving increasing demand for health-focused anti-aging solutions. Bonerge is committed to leveraging BeFisetin®'s superior quality to advance scientific research, foster innovation, and provide consumers with safer and trustworthy products. To be or not to be, that is the question! BeFisetin®: A scientific breakthrough as the world’s first SA-GRAS-certified fisetin ingredient, setting a new industry standard. References [1] Yoon S, Lee H, Kim J, et al. A natural flavonoid, fisetin, alleviates neuroinflammation and memory impairment in D-galactose-treated mice[J]. Frontiers in Pharmacology, 2023, 14: 1134733. [2] Li X, Zhang H, Guo Y, et al. Fisetin promotes osteoblastogenesis and inhibits adipogenesis in bone marrow stromal cells through the activation of the Wnt/β-catenin pathway[J]. International Journal of Molecular Sciences, 2019, 20(23): 5957. [3] Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan[J]. EBioMedicine, 2018, 36: 18-28. [4] Takaya K, Kawaguchi M, Mizutani K, et al. Fisetin, a potential skin rejuvenation drug that eliminates senescent cells in the dermis[J]. Biogerontology, 2023, 24(5): 409-421.

100 Deals associated with Fisetin

External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Meniscus disorder	Phase 3	United States	University of Kentucky	01 Jul 2025
Common Variable Immunodeficiency	Phase 2	United States	Mayo Clinic	12 Apr 2023
Interstitial lung disease due to systemic disease	Phase 2	United States	Mayo Clinic	12 Apr 2023
Carpal Tunnel Syndrome	Phase 2	United States	Mayo Clinic	09 Oct 2022
Post Acute COVID 19 Syndrome	Phase 2	United States	Mayo Clinic	29 Apr 2022
COVID-19	Phase 2	United States	Mayo Clinic	03 Aug 2020
Crouzon Syndrome With Acanthosis Nigricans	Phase 2	United States	Mayo Clinic	06 Feb 2018
Inflammation	Phase 2	United States	Mayo Clinic	06 Feb 2018
IDH1-mutant Glioma	Phase 1	United States	Mayo Clinic	12 Aug 2025
Amyotrophic Lateral Sclerosis	Preclinical	China	First Affiliated Hospital of Harbin Medical University	28 Jun 2025

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04537299 (COVID-FIS, CTgov)	Phase 2	Post Acute COVID 19 Syndrome	20	Fisetin (Treatment Group)	zpfiogurzo(jjqpkzqoro) = yyrtqrorqn gbpyngccus (usaohzdraf, 0.31) View more	-	26 Aug 2025
				Placebo (Placebo Group)	zpfiogurzo(jjqpkzqoro) = atyuhamywe gbpyngccus (usaohzdraf, 0) View more
NCT04210986 (CTgov)	Phase 1/2	Osteoarthritis, Knee	75	Fisetin (Fisetin)	phieelgebg = ciiyfkusjr plqurnaywz (gvxkvrcfnn, rlfbwjnmmb - hyhzbhiemz) View more	-	19 Sep 2024
				Placebo oral capsule (Placebo)	phieelgebg = kcahbvcmfm plqurnaywz (gvxkvrcfnn, njucuogkdo - qwufsoqnvr) View more
NCT04771611 (COVFIS-HOME, CTgov)	Phase 2	COVID-19	55	Fisetin (Treatment Group)	katdqyzkrp = uqzanxjqwj phjyvuammj (bcuzyyaoxj, iyupmywsfd - baxwaybxzp) View more	-	01 Aug 2023
				Placebo (Placebo)	katdqyzkrp = dwxfvglali phjyvuammj (bcuzyyaoxj, whnyftcqtl - ivtnbdnwav) View more

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