{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:29:28Z","timestamp":1793316568931,"version":"4.5.0"},"reference-count":47,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>ICL670A (formerly CGP 72 670) or 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]- benzoic acid is a tridentate iron-selective synthetic chelator of the bis-hydroxyphenyl-triazole class of compounds. The present studies used selective radioiron probes of hepatocellular and reticuloendothelial (RE) iron stores in hypertransfused rats and iron-loaded heart cells to define the source of iron chelated in vivo by ICL670A and its mode of excretion, to examine its ability to remove iron directly from iron-loaded myocardial cells, and to examine its ability to interact with other chelators through a possible additive or synergistic effect. Results indicate that ICL670A given orally is 4 to 5 times more effective than parenteral deferoxamine (DFO) in promoting the excretion of chelatable iron from hepatocellular iron stores. The pattern of iron excretion produced by ICL670A is quite different from that of DFO and all iron excretion is restricted to the bile regardless of whether it is derived from RE or hepatocellular iron stores. Studies in heart cell cultures have shown a favorable interaction between DFO and ICL670A manifested in improved chelating efficiency of ICL670A, which is most probably explained by an exchange of chelated iron between ICL670A and DFO. These unique chelating properties of ICL670A may have practical implications for current efforts to design better therapeutic strategies for the management of transfusional iron overload.<\/jats:p>","DOI":"10.1182\/blood.v97.4.1115","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T08:46:47Z","timestamp":1027759607000},"page":"1115-1122","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":121,"title":["ICL670A: a new synthetic oral chelator: evaluation in hypertransfused rats with selective radioiron probes of hepatocellular and reticuloendothelial iron stores and in iron-loaded rat heart cells in culture"],"prefix":"10.1182","volume":"97","author":[{"given":"Chaim","family":"Hershko","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Shaare Zedek Medical Center, Department of Human Nutrition and Metabolism, Hebrew University Hadassah Medical School, Jerusalem, Israel; Novartis Pharma AG Basel, Basel, Switzerland; and Department of Biological Chemistry, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham M.","family":"Konijn","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Shaare Zedek Medical Center, Department of Human Nutrition and Metabolism, Hebrew University Hadassah Medical School, Jerusalem, Israel; Novartis Pharma AG Basel, Basel, Switzerland; and Department of Biological Chemistry, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Peter","family":"Nick","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Shaare Zedek Medical Center, Department of Human Nutrition and Metabolism, Hebrew University Hadassah Medical School, Jerusalem, Israel; Novartis Pharma AG Basel, Basel, Switzerland; and Department of Biological Chemistry, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Breuer","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Shaare Zedek Medical Center, Department of Human Nutrition and Metabolism, Hebrew University Hadassah Medical School, Jerusalem, Israel; Novartis Pharma AG Basel, Basel, Switzerland; and Department of Biological Chemistry, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvi Ioav","family":"Cabantchik","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Shaare Zedek Medical Center, Department of Human Nutrition and Metabolism, Hebrew University Hadassah Medical School, Jerusalem, Israel; Novartis Pharma AG Basel, Basel, Switzerland; and Department of Biological Chemistry, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Link","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Shaare Zedek Medical Center, Department of Human Nutrition and Metabolism, Hebrew University Hadassah Medical School, Jerusalem, Israel; Novartis Pharma AG Basel, Basel, Switzerland; and Department of Biological Chemistry, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021218152843000_B1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1159\/000203853","article-title":"Results of long-term iron chelating therapy.","volume":"95","author":"Gabutti","year":"1996","journal-title":"Acta Haematol."},{"key":"2020021218152843000_B2","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1056\/NEJM199409013310903","article-title":"Survival of medically treated patients with homozygous \u03b2 thalassemia.","volume":"331","author":"Olivieri","year":"1994","journal-title":"N Eng J Med."},{"key":"2020021218152843000_B3","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1182\/blood.V95.4.1229.004k32_1229_1236","article-title":"Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk \u03b2-thalassemia.","volume":"95","author":"Davis","year":"2000","journal-title":"Blood."},{"key":"2020021218152843000_B4","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1046\/j.1365-2141.1998.00726.x","article-title":"Iron chelators for thalassaemia.","volume":"101","author":"Hershko","year":"1998","journal-title":"Br J Haematol."},{"key":"2020021218152843000_B5","first-page":"O","article-title":"CGP 72 670, a new, potent, orally active iron chelator [abstract]. 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