ArticleJCI insight2022
Small-molecule inhibitor of intestinal anion exchanger SLC26A3 for treatment of hyperoxaluria and nephrolithiasis.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Dietary Oxalate and Intestinal Inflammation: Evidence From Experimental Colitis and Inflammatory Bowel Disease Patient Cohorts.Cellular and molecular gastroenterology and hepatology · 2026Article
- Epithelial plasma membrane transporters as drug targets.Physiological reviews · 2026Review
- Animal models for calcium oxalate kidney stone research.Zoological research · 2026Review
- A novel synbiotic formulation prevents calcium oxalate stones by restoring gut microbiota homeostasis.BMC microbiology · 2025Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Autophagy Regulates Putative Anion Transporter 1 Expression in Intestinal Epithelial Cells.Journal of cellular and molecular medicine · 2025Article
- Magnesium for disease treatment and prevention: emerging mechanisms and opportunities.Trends in pharmacological sciences · 2024Review
- Cell death‑related molecules and targets in the progression of urolithiasis (Review).International journal of molecular medicine · 2024Review
- Substituted 4-methylcoumarin inhibitors of SLC26A3 (DRA) for treatment of constipation and hyperoxaluria.RSC medicinal chemistry · 2024Article
- Mg2+ supplementation treats secretory diarrhea in mice by activating calcium-sensing receptor in intestinal epithelial cells.The Journal of clinical investigation · 2024Article
- Selective isoxazolopyrimidine PAT1 (SLC26A6) inhibitors for therapy of intestinal disorders.RSC medicinal chemistry · 2023Article
- Oxalate Homeostasis in Non-Stone-Forming Chronic Kidney Disease: A Review of Key Findings and Perspectives.Biomedicines · 2023Review
- Small molecule inhibitors of intestinal epithelial anion exchanger SLC26A3 (DRA) with a luminal, extracellular site of action.European journal of medicinal chemistry · 2023Article
- Oxalate homeostasis.Nature reviews. Nephrology · 2023Review
- SLC26 family: a new insight for kidney stone disease.Frontiers in physiology · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Nephrolithiasis is a common and recurrent disease affecting 9% of the US population. Hyperoxaluria is major risk factor for calcium oxalate kidney stones, which constitute two-thirds of all kidney stones. SLC26A3 (DRA, downregulated in adenoma) is an anion exchanger of chloride, bicarbonate, and oxalate thought to facilitate intestinal oxalate absorption, as evidenced by approximately 70% reduced urine oxalate excretion in knockout mice. We previously identified a small-molecule SLC26A3 inhibitor (DRAinh-A270) that selectively inhibited SLC26A3-mediated chloride/bicarbonate exchange (IC50 ~ 35 nM) and, as found here, oxalate/chloride exchange (IC50 ~ 60 nM). In colonic closed loops in mice, luminal DRAinh-A270 inhibited oxalate absorption by 70%. Following oral sodium oxalate loading in mice, DRAinh-A270 largely prevented the 2.5-fold increase in urine oxalate/creatinine ratio. In a mouse model of oxalate nephropathy produced by a high-oxalate low-calcium diet, vehicle-treated mice developed marked hyperoxaluria with elevated serum creatinine, renal calcium oxalate crystal deposition, and renal injury, which were largely prevented by DRAinh-A270 (10 mg/kg twice daily). DRAinh-A270 administered over 7 days to healthy mice did not show significant toxicity. Our findings support a major role of SLC26A3 in intestinal oxalate absorption and suggest the therapeutic utility of SLC26A3 inhibition for treatment of hyperoxaluria and prevention of calcium oxalate nephrolithiasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.