{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T12:06:55Z","timestamp":1794053215590,"version":"4.8.0"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DK126070,DK072517,UL1 TR001872"],"award-info":[{"award-number":["DK126070,DK072517,UL1 TR001872"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of California Drug Discovery Consortium","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["CIL21G0,VERKMA18G0"],"award-info":[{"award-number":["CIL21G0,VERKMA18G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,8]]},"abstract":"<jats:p>\n                    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 (DRA\n                    <jats:sub>inh<\/jats:sub>\n                    -A270) that selectively inhibited SLC26A3-mediated chloride\/bicarbonate exchange (IC\n                    <jats:sub>50<\/jats:sub>\n                    ~ 35 nM) and, as found here, oxalate\/chloride exchange (IC\n                    <jats:sub>50<\/jats:sub>\n                    ~ 60 nM). In colonic closed loops in mice, luminal DRA\n                    <jats:sub>inh<\/jats:sub>\n                    -A270 inhibited oxalate absorption by 70%. Following oral sodium oxalate loading in mice, DRA\n                    <jats:sub>inh<\/jats:sub>\n                    -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 DRA\n                    <jats:sub>inh<\/jats:sub>\n                    -A270 (10 mg\/kg twice daily). DRA\n                    <jats:sub>inh<\/jats:sub>\n                    -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.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.153359","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T12:01:38Z","timestamp":1653393698000},"source":"Crossref","is-referenced-by-count":24,"title":["Small-molecule inhibitor of intestinal anion exchanger SLC26A3 for treatment of hyperoxaluria and nephrolithiasis"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5178-0199","authenticated-orcid":true,"given":"Onur","family":"Cil","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Nephrology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tifany","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Nephrology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3345-2073","authenticated-orcid":true,"given":"Sujin","family":"Lee","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Physiology, UCSF, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Haggie","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Physiology, UCSF, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5054-0078","authenticated-orcid":true,"given":"Alan S.","family":"Verkman","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Physiology, UCSF, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2012.03.052"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000150"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00599.x"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2018.7980"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00240-015-0839-4"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.8"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00488.x"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00373.2018"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfv005"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000518"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2005.06.003"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(03)00403-7"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s00240-016-0952-z"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/ng1762"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00167.2013"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.039818"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00089.2011"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.121370"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01192"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2015.01.024"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1998.274.4.G700"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.147699"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.207"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00488.2015"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3845"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2019.106609"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.401"},{"key":"B28","unstructured":"Litholink Laboratory Reporting System. 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