Uriadec (topiroxostat) / Fuji Yakuhin, Suzuken - LARVOL DELTA

Efficacy and safety of urate-lowering therapies in asymptomatic hyperuricaemia: a systematic review and network meta-analysis of key clinical outcomes. (PubMed, Ann Med) - "Random-effects modelling showed that, compared to controls, Verinurad_Febuxostat (P-score = 0.82; pooled mean difference [95% CI]: -3.20 [-4.76 to -1.64]) was the most effective in reducing SUA, Febuxostat (P-score = 0.78; 1.91 [0.47 to 3.35]) was the most effective in improving eGFR, Topiroxostat (P-score = 0.96; -6.10 [-11.75 to -0.45]) was most effective in improving SBP, and Febuxostat (P-score = 0.78; 0.77 [0.61 to 0.98]) reduced the risk of CREs most effectively. The Confidence in Network Meta-Analysis (CINeMA) assessment indicated that the overall quality of evidence was low to moderate. Available evidence suggests that febuxostat not only plays a significant role in lowering SUA levels but also significantly delays the decline in eGFR and reduces the risk of CREs."

Clinical • Clinical data • Journal • Retrospective data • Review • Cardiovascular • Chronic Kidney Disease • Hepatology • Liver Failure • Metabolic Disorders • Nephrology • Renal Disease • CRP

Searching for potential xanthine oxidase inhibitors from Vietnamese herb plants via computational studies. (PubMed, Comput Biol Chem) - "Five newly discovered compounds, namely salvianolic acid A, puerarol, ochnaflavone, and forsythensides A and B, showed lower predicted binding energies than topiroxostat, suggesting their potential for further exploration as putative XO inhibitors...The residues Glu802, Arg880, Thr1010, and Glu1261 served as key contributors to ligand binding, forming strong hydrogen bonds and side-chain contacts with the inhibitors. These findings offer valuable mechanistic insights into the interaction between natural compounds and XO, and highlight potential candidates for the development of novel XO inhibitors."

Journal • Gout • Immunology • Inflammatory Arthritis • Rheumatology

NEW PHARMACOLOGICAL STRATEGIES FOR PEDIATRIC CHRONIC KIDNEY DISEASE (ESPN 2025) - "Since existing xanthine oxidase inhibitors are excreted by the kidneys, there is a risk of serious side effects in patients with impaired renal function.△ However, newer urate-lowering agents such as febuxostat and topiroxostat, introduced in the 2010s, lack a purine structure and can be administered to patients with moderate renal dysfunction. The renal protective effects of drugs may differ between children and adults, and a treatment plan that takes into account the age and characteristics of the drug is necessary."

Clinical • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Pediatrics • Renal Disease

Impact of Urate-Lowering Agents on Renal Outcomes in Chronic Kidney Disease: A Systematic Review. (PubMed, Cureus) - "Ten studies met the inclusion criteria, assessing allopurinol, febuxostat, verinurad, and topiroxostat. While febuxostat may slow CKD progression in select populations, evidence for allopurinol and combination therapies remains inconclusive. Heterogeneity in outcomes underscores the need for personalized treatment and further research to identify optimal candidates for ULA therapy."

Journal • Review • Chronic Kidney Disease • Nephrology • Renal Disease

LEFT ATRIAL SEPTAL POUCH THROMBUS PROHIBITING TRANS-SEPTAL PUNCTURE FOR LEFT ATRIAL APPENDAGE CLOSURE - FAILING TO PLAN IS PLANNING TO FAIL - Ramy Abdelmaseih (ACC 2025) - "We present a case of aborted left atrial appendage closure (LAAC) after identifying LASP thrombus on CT and TEE imagesCase: An 89-year-old female with history of long-standing persistent atrial fibrillation on anticoagulation; CHA2DS2-VASc 3 and HAS-BLED 4, referred for LAAC evaluation due to recurrent hematuriaDecision-making: The patient was deemed a poor candidate for long-term anticoagulation... Attentive evaluation of interatrial septum while reviewing preprocedural cardiac scans is crucial for a prompt identification of LASP thrombus. Trans-septal approach should be avoided in such cases to avoid cardioembolic complications. To date, only a handful of cases have described LASP thrombus"

Atrial Fibrillation • Thrombosis

Cardiovascular Events During Treatment With Xanthine Oxidoreductase Inhibitors in Patients With Gout and Hyperuricemia in Japan　- A JMDC Claims Database Study. (PubMed, Circ Rep) - "Adjusted risks of atrial fibrillation, heart failure, dialysis, total cardiovascular events, and total cardiovascular + renal events were significantly higher with febuxostat vs. allopurinol. Topiroxostat may provide a better tolerated option for the treatment of hyperuricemia and/or gout in Japanese patients with respect to cardiovascular events."

Journal • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Gout • Heart Failure • Inflammatory Arthritis • Rheumatology

Comparison of the incidence of proteinuria and changes in eGFR among febuxostat and topiroxostat users. (PubMed, Clin Exp Nephrol) - "Topiroxostat prevalent users had a lower risk of proteinuria than febuxostat prevalent users in non-diabetic individuals with eGFR ≥ 60 mL/min/1.73 m2. Our findings suggest that topiroxostat might be more effective than febuxostat in preventing proteinuria in non-diabetic individuals with eGFR ≥ 60 mL/min/1.73 m2."

Journal • Cardiovascular • Renal Disease

Reno-protective effects of xanthine oxidase inhibitors in patients with type 2 diabetes and chronic kidney disease: a systematic review and meta-analysis. (PubMed, J Nephrol) - "This study suggests the potential of febuxostat or topiroxostat to delay renal function decline in patients with diabetes and underlying renal impairment, that needs to be confirmed in further studies."

Journal • Retrospective data • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Characterizing Pharmacokinetic Variability of Topiroxostat in Chinese Population: Insights from a Phase I Randomized Clinical Trial. (PubMed, Curr Drug Metab) - "The trial successfully established the pharmacokinetic parameters of topiroxostat in a Chinese population, confirming its safety and efficacy. The results support the need for individualized dosing strategies and optimize therapeutic outcomes."

Clinical • Journal • P1 data • PK/PD data

Topiroxostat-A Safer Uricostatic Drug with Enhanced Renal Protection: A Narrative Review. (PubMed, J Assoc Physicians India) - " Topiroxostat shows promise as an efficient and safe renoprotective agent in patients, irrespective of renal disease status. However, further large-scale, long-term, and multicenter clinical studies are needed to generate high-quality evidence in different populations and settings."

Journal • Review • Gout • Inflammatory Arthritis • Nephrology • Renal Disease • Rheumatology • FABP1

Insights into the modulatory effects of host-gut microbial xanthine co-metabolism on high-fat diet-fed mice. (PubMed, Biochem Pharmacol) - "Here, we explored the role of host-gut microbial xanthine co-metabolism in the prevention and treatment of HFD-induced obesity by orally administration of Bifidobacterium longum, xanthine, and a xanthine oxidase inhibitor (topiroxostat)...Untargeted metabolomics analysis implied that xanthine might serve as a crucial molecule in regulating body weight, exerting a preventive effect on HFD-induced obesity. This study offers new perspectives on the influence of host-gut microbial xanthine co-metabolism on HFD-fed mice and emphasizes the promising role of xanthine in promoting weight loss."

Journal • Preclinical • Genetic Disorders • Obesity

Allopurinol, Febuxostat, and Nonuse of Xanthine Oxidoreductase Inhibitor Treatment in Patients Receiving Hemodialysis: A Longitudinal Analysis. (PubMed, Kidney Med) - "Data of 6,791 patients who had no history of topiroxostat usage and underwent maintenance hemodialysis between March 2016 and March 2019 at Yokohama Daiichi Hospital, Zenjinkai, and its affiliated dialysis clinics in Japan's Kanagawa and Tokyo metropolitan areas were collected. Allopurinol and febuxostat improved survival for all-cause mortality. Allopurinol and not febuxostat reduced the risk of CVD events, HF, and AMI."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction

A comprehensive review of synthetic and semisynthetic xanthine oxidase inhibitors: identification of potential leads based on in-silico computed ADME characteristics. (PubMed, Mol Divers) - "Marketed available XO inhibitors (allopurinol, febuxostat, and topiroxostat) are used to treat hyperuricemia but they are associated with fatal side effects, which pose serious problems for the healthcare system, rising the need for new, more potent, safer compounds. This review summarizes recent findings on XO and describes their design, synthesis, biological significance in the development of anti-hyperuricemic drugs with ADME profile, structure activity relationship (SAR) and molecular docking studies. The results might help medicinal chemists to develop more efficacious XO inhibitors."

Journal • Review • Alzheimer's Disease • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Diabetes • Gout • Inflammatory Arthritis • Metabolic Disorders • Nephrology • Renal Disease • Rheumatology

Topiroxostat improves glomerulosclerosis in type 2 diabetic Nagoya Shibata Yasuda mice with early nephropathy. (PubMed, Eur J Pharmacol) - "Renal MDA levels were lower in the NSY+topiroxostat group than in the HFD control group. Topiroxostat can reduce glomerular sclerosis, and the reduction is associated with renal oxidative markers."

Journal • Preclinical • Diabetes • Diabetic Nephropathy • Glomerulonephritis • Nephrology • Oncology • Renal Disease • Type 2 Diabetes Mellitus • CST3 • GPX2 • PRDX1 • SOD3

Xanthine oxidase immobilized cellulose membrane-based colorimetric biosensor for screening and detecting the bioactivity of xanthine oxidase inhibitors. (PubMed, Int J Biol Macromol) - "Xanthine oxidase (XO) is a typical target for hyperuricemia and gout, for which there are only three commercial xanthine oxidase inhibitors (XOIs): febuxostat, topiroxostat and allopurinol. Most importantly, the XNCM was able to quantitatively detect the IC50 values of two commercial inhibitors (febuxostat and allopurinol). All the results confirmed that the XNCM is a simple and effective tool which can be used for the accelerated screening of XOIs and has the potential to uncover additional XOIs."

Journal • Gout • Inflammatory Arthritis • Rheumatology

Comparison of the incidence of proteinuria and eGFR change between febuxostat and topiroxostat users (ERA-EDTA 2024) - "The topiroxostat prevalent-users had a lower risk of the incidence of proteinuria than the febuxostat prevalent-users in the non-diabetic individuals with eGFR ≥60 mL/min/1.73 m2. Our findings suggested that topiroxostat might be more effective than febuxostat in preventing proteinuria in non-diabetic individuals with eGFR ≥60 mL/min/1.73 m2."

Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Hypertension • Metabolic Disorders • Renal Disease

Evaluation of the inhibitory effects of antigout drugs on human carboxylesterases in vitro. (PubMed, Toxicol In Vitro) - "The present study aimed to evaluate the inhibitory effect of antigout drugs (allopurinol, febuxostat, topiroxostat, benzbromarone, lesinurad and probenecid) on the activity of the crucial phase I drug-metabolizing enzymes, carboxylesterases (CESs). In silico docking showed that hydrogen bonds and hydrophobic interactions contributed to the intermolecular interactions of antigout drugs on CESs. Therefore, vigilant monitoring of potential drug-drug interactions (DDIs) is imperative when co-administering antigout drugs in clinical practice."

Journal • Preclinical • Cardiovascular • Chronic Kidney Disease • Gout • Inflammatory Arthritis • Metabolic Disorders • Nephrology • Renal Disease • Rheumatology

Drug Repositioning via Graph Neural Networks: Identifying Novel JAK2 Inhibitors from FDA-Approved Drugs through Molecular Docking and Biological Validation. (PubMed, Molecules) - "Based on these predictions, ribociclib, topiroxostat, amodiaquine, and gefitinib were identified as potential JAK2 inhibitors...To further validate these findings and confirm their JAK2 inhibitory activity, molecular docking experiments were conducted using tofacitinib-an FDA-approved drug for JAK2 inhibition...In conclusion, our study highlights how deep learning models can significantly enhance virtual screening efforts in drug discovery by efficiently identifying potential candidates for specific targets such as JAK2. These newly discovered drugs hold promises as novel JAK2 inhibitors deserving further exploration and investigation."

FDA event • Journal

Multicenter randomized controlled trial of intensive uric acid lowering therapy for CKD patients with hyperuricemia: TARGET-UA. (PubMed, Clin Exp Nephrol) - "This study did not reveal the benefit of Intensive ULT to improve albuminuria levels. (UMIN000026741 and jRCTs051180146)."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Xanthine oxidase inhibitors treatment or discontinuation effects on mortality: evidence of xanthine oxidase inhibitors withdrawal syndrome. (PubMed, Front Pharmacol) - "In the sub-analysis, the group with allopurinol (OR, 0.578; 95% CI, 0.557-0.600), febuxostat (OR, 0.610; 95% CI, 0.599-0.622), and topiroxostat (HR, 0.545; 95% CI, 0.473-0.628) showed lower OR of mortality compared with that without any urate-lowering agent. Conversely, XOI withdrawal is linked to elevated mortality risk. This emphasizes the importance of both prescribing and discontinuing XOI carefully to optimize patient outcomes."

Journal • Acute Coronary Syndrome • Cardiovascular • Congestive Heart Failure • Heart Failure

Timing of Initiation of Xanthine Oxidase Inhibitors Based on Serum Uric Acid Level Does Not Predict Renoprognosis in Patients with Preserved Kidney Function. (PubMed, Metab Syndr Relat Disord) - " Early initiation of XOIs did not predict a significant benefit on renoprognosis even among the population with preserved kidney function. The validity of initiating XOIs with the aim of improving renoprognosis based on sUA is questionable."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Human Cardiovascular Disease Model Provides Transcriptomic Evidence of Cardiovascular Risk Associated with Febuxostat (ACR Convergence 2023) - " Febuxostat significantly modulated more signaling pathways associated with cell stress and cardiovascular risk than allopurinol or topiroxostat, gout medications not associated with increased cardiovascular risk. Together, these data support the FDA warning for febuxostat and suggest that cardiovascular risk associated with gout medications stems from chemical structure of the medication, itself, rather than the target, xanthine oxidase."

Cardiovascular • Gout • Immunology • Inflammatory Arthritis • Rheumatology

Past, present and future of xanthine oxidase inhibitors: design strategies, structural and pharmacological insights, patents and clinical trials. (PubMed, RSC Med Chem) - "Elevation of xanthine oxidase is not only the prime cause of gout but is also responsible for various hyperuricemia associated pathological conditions like diabetes, chronic wounds, cardiovascular disorders, Alzheimer's disease, etc. Currently available xanthine oxidase inhibitors in clinical practice (allopurinol, febuxostat and topiroxostat) suffer from fatal side effects that pose a serious problem to the healthcare system, raising global emergency to develop novel, potent and safer xanthine oxidase inhibitors. Information generated in this review has suggested fragment-based drug design (FBDD) and molecular hybridization techniques to be most suitable for development of desired xanthine oxidase inhibitors as one provides high selectivity toward the enzyme and the other imparts multifunctional properties to the structure and both may possess capabilities to surpass the limitations of currently available clinical drugs. All in combination will exclusively update..."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Diabetes • Gout • Inflammatory Arthritis • Metabolic Disorders • Rheumatology

Urate-Lowering Drugs And Muscle Injury: A Systematic Review and Network Meta-Analysis. (PubMed, J Clin Pharmacol) - "No statistically significant differences were found between placebo and six urate-lowering therapies: allopurinol (risk ratio [RR] 1.05, 95% confidence interval [CI] 0.63-1.73), febuxostat (RR 1.10, 95% CI 0.71-1.70), lesinurad (RR 7.00, 95% CI 0.31-160.36), lesinurad concomitant with allopurinol (RR 0.85, 95% CI 0.34-2.11), lesinurad concomitant with febuxostat (RR 1.97, 95% CI 0.55-7.03), and topiroxostat (RR 0.99, 95% CI 0.37-2.65). No statistically significant differences were found between placebo and six urate-lowering therapies: allopurinol (risk ratio [RR] 1.05, 95% confidence interval [CI] 0.63-1.73), febuxostat (RR 1.10, 95% CI 0.71-1.70), lesinurad (RR 7.00, 95% CI 0.31-160.36), lesinurad concomitant with allopurinol (RR 0.85, 95% CI 0.34-2.11), lesinurad concomitant with febuxostat (RR 1.97, 95% CI 0.55-7.03), and topiroxostat (RR 0.99, 95% CI 0.37-2.65). The findings suggest that there is little need to consider the risk of muscle injury when using..."

Journal • Retrospective data • Review

Computational Characterization of the Inhibition Mechanism of Xanthine Oxidoreductase by Topiroxostat. (PubMed, ACS Catal) - "Calculated results for the proposed reaction mechanisms for each metabolite's inhibition reaction in the enzyme's active site, binding affinities, and the noncovalent interactions with the surrounding amino acid residues are consistent with previously reported experimental findings. Analysis of the noncovalent interactions via energy decomposition analysis (EDA) and noncovalent interaction (NCI) techniques suggests that residues L648, K771, E802, R839, L873, R880, R912, F914, F1009, L1014, and A1079 can be used as key interacting residues for further hybrid-type inhibitor development."

Journal • Gout • Inflammatory Arthritis • Rheumatology