- |||||||||| verinurad (RDEA3170) / AstraZeneca, Zurampic (lesinurad) / AstraZeneca, probenecid / Generic mfg.
Journal: Virtual screening and biological evaluation of natural products as urate transporter 1 (URAT1) inhibitors. (Pubmed Central) - Dec 4, 2025 The results showed that the carbonyl group on C-4 and hydroxyl group on C-7, C-4', and C-5' in flavonoids were conducive for URAT1 inhibitory effects. This study facilitates the application of flavonoids in the development of URAT1 inhibitors.Communicated by Ramaswamy H. Sarma.
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Journal: Structural Basis for Inhibition of Urate Reabsorption in URAT1. (Pubmed Central) - Mar 28, 2025 The three small molecules reside in the URAT1 central cavity with different binding modes, locking URAT1 in an inward-facing conformation. This study provides mechanistic insights into the drug modulation of URAT1 and sheds light on the rational design of potential URAT1-specific therapeutics for treating hyperuricemia.
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Journal, Machine learning: Crystal structure validation of verinurad via proton-detected ultra-fast MAS NMR and machine learning. (Pubmed Central) - Sep 22, 2024 To do this, we take advantage of 1H resolution improvement at ultra-fast MAS and use solely 1H-detected experiments and machine learning methods to assign all the experimental proton and carbon chemical shifts. This framework provides a new tool for elucidating chemical information from crystalline samples with limited sample volume and yields remarkably faster acquisition times compared to 13C-detected experiments, without the need to employ dynamic nuclear polarization.
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Journal: Verinurad does not prolong QTc interval: A thorough QT study using concentration-QTc modelling. (Pubmed Central) - Dec 13, 2022 P1 In vivo, isobavachin exhibited powerful urate-lowering and uricosuric effects at 5-20 As the effect on ΔΔQTcF was below the threshold for regulatory concern (10 msec) at the supratherapeutic exposure, it can be concluded that verinurad and allopurinol treatment does not induce QTcF prolongation at the highest clinically relevant exposures.
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Journal: Considerations for Choosing First-Line Urate-Lowering Treatment in Older Patients with Comorbid Conditions. (Pubmed Central) - Nov 28, 2022 The combination therapy of a novel uricosuric, verinurad, plus febuxostat reduced albuminuria in hyperuricemic patients with type 2 diabetes and CKD in a phase 2a trial, and further RCTs are awaited. Finally, the sodium-glucose cotransporter-2 inhibitor class of oral hypoglycemic agents, known to exert beneficial CV and renal effects independent of glycemic control, have shown a uricosuric effect and could be used as adjunctive therapy in older patients with cardiorenal comorbidities.
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Urate Regulates Mitochondrial Function in a URAT1 Dependent Manner in Renal Epithelial Cells (Exhibit Hall, Orange County Convention Center, West Building) - Oct 13, 2022 - Abstract #KIDNEYWEEK2022KIDNEY_WEEK_1857; Both effects were abolished in the presence 0.5μM of verinurad. Conclusion We conclude that increased tubular urate alters intracellular lactate levels and mitochondrial function in a URAT1 dependent manner, providing mechanistic evidence that urate alters cell metabolism in the proximal tubule and may contribute to kidney disease progression.
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Clinical, P2b data, Journal: Rationale, design, demographics, and baseline characteristics of the randomised, controlled, phase 2b SAPPHIRE study of verinurad plus allopurinol in patients with chronic kidney disease and hyperuricaemia. (Pubmed Central) - Jul 30, 2022 P2, P2b The present findings will provide further comprehensive insight into the treatment value of certain uricosuric agents for gout or hyperuricemia. This study will assess the combined clinical effect of verinurad + allopurinol on kidney function in patients with CKD, hyperuricaemia and albuminuria, and whether this combination confers renoprotection beyond standard-of-care.
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Trial completion: AMETHYST: Study of Verinurad in Heart Failure With Preserved Ejection Fraction (clinicaltrials.gov) - Jun 1, 2022 P2, N=159, Completed, This study will assess the combined clinical effect of verinurad + allopurinol on kidney function in patients with CKD, hyperuricaemia and albuminuria, and whether this combination confers renoprotection beyond standard-of-care. Active, not recruiting --> Completed
- |||||||||| verinurad (RDEA3170) / AstraZeneca, Zurampic (lesinurad) / AstraZeneca
Characterization of the uric acid transporter URAT1 (SLC22A12) in platelets and megakaryocytes (Exhibition) - May 13, 2022 - Abstract #ISTH2022ISTH_1045; Cell fractionation experiments were consistent with flow cytometry results. Incubation of washed platelets with uric acid (50-100 µg/ml) did not induce spontaneous platelet aggregation, nor did it induce synergistic effects in the presence of low concentrations of classical platelet agonists.
- |||||||||| Journal: What's new on the front-line of gout pharmacotherapy? (Pubmed Central) - Feb 26, 2022
Novel uricosurics are a class for continued drug development; verinurad and arhalofenate are agents with future promise...Its immunogenicity significantly threatens the achievement of sustained urate lowering responses. Abrogating pegloticase's immunogenicity with immunomodulatory co-therapy may lend to sustained efficacy.
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Clinical, Journal: A semi-mechanistic exposure-response model to assess the effects of verinurad, a potent URAT1 inhibitor, on serum and urine uric acid in patients with hyperuricemia-associated diseases. (Pubmed Central) - Jan 29, 2022 The potencies (EC50s) of verinurad (reducing uric acid reuptake), febuxostat (reducing uric acid production), and oxypurinol (reducing uric acid production) were: 29, 128, and 13,030 ng/mL, respectively...Simulations based on the uric acid model were performed to assess dose-response of verinurad in combination with XOI, and to investigate the impact of covariates. The simulations demonstrated application of the model to support dose selection for verinurad.
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Review, Journal: A historical journey of searching for uricosuric drugs. (Pubmed Central) - Jan 6, 2022 Pharmacotherapeutically, a negative urate balance should be the aim of clinicians and then the rational choice of treatment with uricosurics seems quite logical and promising, but has not had a thorough attention of pharma, researchers nor of clinicians, though most gout patients were and still are low excretors. Here, an overview on the 70-year-old journey mankind has made in a search for uricosurics resulting so far in only 1 registered uricosuric per continent.
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Trial completion date, Trial primary completion date: AMETHYST: Study of Verinurad in Heart Failure With Preserved Ejection Fraction (clinicaltrials.gov) - Nov 15, 2021 P2, N=159, Active, not recruiting, Using in vitro systems recommended by regulatory agencies, we determined that, apart from verinurad being a substrate of OATP1B3, the potential for clinically relevant drug-drug interactions involving verinurad and its metabolites M1 and M8 as victims or perpetrators of metabolizing enzymes or drug transporters is considered low. Trial completion date: Nov 2022 --> Apr 2022 | Trial primary completion date: Nov 2022 --> Apr 2022
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Journal: In Reply to "Verinurad/Febuxostat and Nephrotoxicity". (Pubmed Central) - Sep 11, 2021 Dapagliflozin further reduced sUA without influencing uUA excretion, suggesting that its combination with verinurad and febuxostat at the doses tested does not adversely affect kidney function. No abstract available
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