vutiglabridin (HSG4112) / Glaceum - LARVOL DELTA

Targeting PON2 with Vutiglabridin Restores Mitochondrial Integrity and Attenuates Oxidative Stress-Induced Senescence. (PubMed, Antioxidants (Basel)) - "The present study demonstrates that vutiglabridin alleviates oxidative stress-induced cellular senescence by preserving mitochondrial integrity and redox balance via a PON2-dependent mechanism. This study lends further support to the investigation of the PON2 pathway as a therapeutic target in age-related cellular dysfunction."

Journal • Metabolic Disorders • CDKN1A

Vutiglabridin ameliorates obesity by directly reducing fat mass through AMPK/lipophagy activation in adipocytes. (PubMed, Biomed Pharmacother) - "Multi-omics analyses, including proteomic and transcriptomic profiling of epididymal WAT in DIO-mice, further confirmed this mechanism. Collectively, these findings demonstrate that VUTI represents a promising therapeutic strategy for obesity by inducing fat-selective reduction via AMPK-mediated lipophagy."

Journal • Genetic Disorders • Obesity • AMPK

Neurotherapeutic effects of Vutiglabridin as a Paraoxonase-2 modulator in preclinical models of Parkinson's disease. (PubMed, Mol Neurodegener) - "These findings indicate that Vutiglabridin may serve as a promising therapeutic approach for reducing reactive oxygen species (ROS) levels by modulating PON2 activity in Parkinson's diseases."

Journal • Preclinical • CNS Disorders • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease

Pharmacokinetics, pharmacodynamics and safety of vutiglabridin after multiple oral administrations in healthy female and obese subjects. (PubMed, Br J Clin Pharmacol) - "Vutiglabridin presented higher peak plasma concentrations but lower systemic exposure in obese subjects than in healthy females. Additionally, a modest downward trend in body weight was observed in obese subjects relative to healthy female subjects. These findings support further long-term phase II clinical trials."

Clinical • Journal • PK/PD data • Genetic Disorders • Inflammation • Obesity

A Study to Assess the Efficacy and Safety of Vutiglabridin in Knee Osteoarthritis Patients (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Glaceum | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Osteoarthritis • Pain • Rheumatology

Enhancing Mitochondrial Function to Mitigate RPE Senescence (ARVO 2025) - "Its effects relied on a protective protein, PON2. Vutiglabridin shows promise as a potential AMD therapy targeting RPE aging."

Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • CDKN2A

Targeting Paraoxonase-2: A potential strategy to mitigate cigarette smoke-induced RPE mitochondrial dysfunction and retinal degeneration. (ARVO 2025) - "PON2 silencing and pharmacological upregulation using either vutiglabridin (VG) or HM-10/10 were utilized in mechanistic studies...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Age-related Macular Degeneration • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders

A Study to Assess the Efficacy and Safety of Vutiglabridin in Early Parkinson's Disease Patients (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Glaceum | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Movement Disorders • Parkinson's Disease

A Study to Assess the Efficacy and Safety of Vutiglabridin in Knee Osteoarthritis Patients (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Glaceum

New P2 trial • Immunology • Osteoarthritis • Pain • Rheumatology

Paraoxonase-2 agonist vutiglabridin promotes autophagy activation and mitochondrial function to alleviate non-alcoholic steatohepatitis. (PubMed, Br J Pharmacol) - "Our data demonstrated that VUTI is a promising therapeutic for NASH. Targeting PON2 may be important for improving liver function in various immune-metabolic diseases including NASH."

Journal • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

A Study to Assess the Efficacy and Safety of Vutiglabridin in Early Parkinson's Disease Patients (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Glaceum

New P2 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

A Study to Investigate the Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Characteristics and Food Effect of HSG4112 in High Doses (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Glaceum | Recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

A Study to Evaluate the Safety and Efficacy of HSG4112 in Overweight and Obese Patients (clinicaltrials.gov) - P2 | N=81 | Completed | Sponsor: Glaceum | Active, not recruiting ➔ Completed | Phase classification: P2a ➔ P2 | Trial completion date: Dec 2022 ➔ Apr 2023

Phase classification • Trial completion • Trial completion date • Genetic Disorders • Obesity

Effects of meal type on the bioavailability of vutiglabridin, a novel anti-obesity agent, in healthy subjects. (PubMed, Clin Transl Sci) - "The study drug was well-tolerated after administration in both the fed and fasted states. Food ingestion substantially increased the extent of oral vutiglabridin absorption in healthy subjects, and this enhancement increased with the fat content of the meal."

Journal • Genetic Disorders • Obesity

Vutiglabridin Alleviates Cellular Senescence with Metabolic Regulation and Circadian Clock in Human Dermal Fibroblasts. (PubMed, Antioxidants (Basel)) - "Our results demonstrate the significant senescence-alleviating effects of vutiglabridin, specifically with the restoration of cellular circadian rhythmicity and metabolic regulation. These data support the potential development of vutiglabridin against aging-associated diseases and corroborate the intricate link between cellular senescence, metabolism, and the circadian clock."

Journal • Genetic Disorders • Obesity • ARNTL • CDKN1A • CDKN2A

Effect of anti-obesity agent HSG4112 on overweight and obese patients following 12 weeks of oral treatment: a study protocol for a randomised, double-blind, placebo-controlled, parallel-group, phase 2a clinical trial. (PubMed, Front Pharmacol) - P2a | "This trial will evaluate the efficacy and safety of HSG4112 in overweight and obese adults. Upon proving the safety and effectiveness of the newly developed mechanism, it might significantly improve the perception of the product among medical personnel and obese patients. Furthermore, it may aid in managing chronic conditions that require long-term treatment. Trial registration: ClinicalTrials.gov, identifier [NCT05197556]."

Journal • P2a data • Genetic Disorders • Obesity

Vutiglabridin exerts anti-ageing effects in aged mice through alleviating age-related metabolic dysfunctions. (PubMed, Exp Gerontol) - "Vutiglabridin slows metabolic ageing mechanisms such as decreased insulin sensitivity, increased inflammation, and altered NAD metabolism in adipose tissue in mice experiments, while also retaining muscle homeostasis, which is deteriorated with age. It also improves the lipid profile in the blood and restores mitochondrial function in the liver to reduce ROS generation."

Journal • Preclinical • Inflammation • Metabolic Disorders • CDKN1A • CDKN2A

Vutiglabridin Modulates Paraoxonase 1 and Ameliorates Diet-Induced Obesity in Hyperlipidemic Mice. (PubMed, Biomolecules) - "We further investigated the effects of vutiglabridin in obese and hyperlipidemic LDLR mice and found that it significantly increases plasma PON1 levels, while decreasing body weight, total fat mass, and plasma cholesterol levels. Overall, our results demonstrate that PON1 is a direct, interacting target of vutiglabridin, and that the modulation of PON1 by vutiglabridin may provide benefits for the treatment of hyperlipidemia and obesity."

Journal • Preclinical • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • PON1

Vutiglabridin, a mitochondrial paraoxonase-2 modulator, attenuates laser-induced choroidal neovascularization in mice in a manner comparable and complementary to anti-VEGF (ARVO 2023) - "Our findings show promise of a drug that can be taken orally, can be as effective as the current injection drugs, and can be combined with them to provide even greater benefits to wet AMD patients. It should urgently undergo the required clinical trials."

Preclinical • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • HIF1A • IL1B • IL6

Synthetic Glabridin Derivatives Inhibit LPS-Induced Inflammation via MAPKs and NF-κB Pathways in RAW264.7 Macrophages. (PubMed, Molecules) - "In the previous study, we synthesized glabridin derivatives-HSG4112, (S)-HSG4112, and HGR4113-based on the structure-activity relationship study of glabridin to improve its biological efficacy and chemical stability. In addition, the compounds increased the expression of antioxidant protein heme oxygenase (HO-1) by inducing nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) through ERK and p38 MAPKs. Taken together, these results indicate that the synthetic glabridin derivatives exert strong anti-inflammatory effects in LPS-stimulated macrophages through MAPKs and NF-κB pathways, and support their development as potential therapeutics against inflammatory diseases."

Journal • Inflammation • Oncology • IL1B • IL6 • NF-κβ • PTGS2 • TNFA

VUTIGLABRIDIN, AN ANTI-OBESITY DRUG CANDIDATE, MODULATES A NOVEL TARGET PROTEIN PARAOXONASE-2 (PON2) FOR PROTECTION OF DOPAMINERGIC NEURONS AGAINST MITOCHONDRIAL DYSFUNCTION. (ADPD 2023) - P2a | "Our results demonstrate that vutiglabridin is neuroprotective via PON2 and provide support for the immediate clinica l development of vutiglabridin as a novel PON2 modulator for the treatment of PD."

CNS Disorders • Genetic Disorders • Metabolic Disorders • Movement Disorders • Obesity • Parkinson's Disease

A Study to Investigate the Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Characteristics and Food Effect of HSG4112 in High Doses (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Glaceum | Not yet recruiting ➔ Recruiting | Trial primary completion date: May 2023 ➔ Dec 2022

Enrollment open • Trial primary completion date • Genetic Disorders • Obesity • CCL2 • IL6 • TNFA

A Study to Investigate the Safety and Pharmacokinetic/Pharmacodynamic Characteristics of HSG4112 (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Glaceum | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity • CCL2 • IL6 • TNFA

A Study to Evaluate the Safety and Efficacy of HSG4112 in Overweight and Obese Patients (clinicaltrials.gov) - P2a | N=81 | Active, not recruiting | Sponsor: Glaceum | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

A Study to Investigate the Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Characteristics and Food Effect of HSG4112 in High Doses (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Glaceum

New P1 trial • Genetic Disorders • Obesity • CCL2 • IL6 • TNFA