{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:57Z","timestamp":1787013957391,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2015,6,26]],"date-time":"2015-06-26T00:00:00Z","timestamp":1435276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Janssen Pharmaceutical Research and Development"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,8]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n Small\u2010molecule inhibitors of prolyl hydroxylase (\n PHD<\/jats:styled-content>\n ) enzymes are a novel target for the treatment of anaemia and functional iron deficiency (\n FID<\/jats:styled-content>\n ). Other than being orally bioavailable, the differentiation of\n PHD<\/jats:styled-content>\n inhibitors from recombinant human erythropoietin (\n rhEPO<\/jats:styled-content>\n ) has not been demonstrated.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n JNJ<\/jats:styled-content>\n \u201042905343 was identified and characterized as a novel inhibitor of\n PHD<\/jats:styled-content>\n and its action was compared with\n rhEPO<\/jats:styled-content>\n in healthy rats and in a rat model of inflammation\u2010induced anaemia and\n FID<\/jats:styled-content>\n [peptidoglycan\u2010polysaccharide (\n PGPS<\/jats:styled-content>\n ) model].\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n Oral administration of\n JNJ<\/jats:styled-content>\n \u201042905343 to healthy rats increased the gene expression of cytochrome b (\n DcytB<\/jats:styled-content>\n ) and divalent metal\u2010ion transporter 1 (\n DMT1<\/jats:styled-content>\n ) in the duodenum, and increased plasma\n EPO<\/jats:styled-content>\n . Repeated administration of\n JNJ<\/jats:styled-content>\n \u201042905343 for 28 days increased blood haemoglobin, mean corpuscular haemoglobin (\n MCH<\/jats:styled-content>\n ) and mean corpuscular volume (\n MCV<\/jats:styled-content>\n ). The serum iron concentration was increased with low doses (0.3\u2009mg\u00b7kg\n \u22121<\/jats:sup>\n ) but reduced at high doses (6\u2009mg\u00b7kg\n \u22121<\/jats:sup>\n ). In\n PGPS<\/jats:styled-content>\n \u2010treated rats, administration of\n JNJ<\/jats:styled-content>\n \u201042905343 for 28 days corrected\n FID<\/jats:styled-content>\n and anaemia, as reflected by increased blood haemoglobin,\n MCH<\/jats:styled-content>\n and\n MCV<\/jats:styled-content>\n . Increased expression of\n \n DcytB<\/jats:italic>\n <\/jats:styled-content>\n and\n DMT1<\/jats:italic>\n genes in the duodenum resulting in increased iron availability was defined as the mechanism for these effects. rhEPO did not affect\n DcytB<\/jats:styled-content>\n and\n DMT1<\/jats:styled-content>\n and was not effective in\n PGPS<\/jats:styled-content>\n \u2010treated rats.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Implications<\/jats:title>\n \n PHD<\/jats:styled-content>\n inhibition has a beneficial effect on iron metabolism in addition to stimulating the release of\n EPO<\/jats:styled-content>\n . Small\u2010molecule inhibitors of\n PHD<\/jats:styled-content>\n such as\n JNJ<\/jats:styled-content>\n \u201042905343 represent a mechanism distinct from\n rhEPO<\/jats:styled-content>\n to treat anaemia and\n FID<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.13188","type":"journal-article","created":{"date-parts":[[2015,5,18]],"date-time":"2015-05-18T23:51:20Z","timestamp":1431993080000},"page":"4078-4088","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Prolyl hydroxylase inhibition corrects functional iron deficiency and inflammation\u2010induced anaemia in rats"],"prefix":"10.1111","volume":"172","author":[{"given":"Terrance D","family":"Barrett","sequence":"first","affiliation":[{"name":"Cardiovascular Metabolic Research Janssen Pharmaceutical Companies of Johnson & Johnson San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjin","family":"Gao","sequence":"additional","affiliation":[{"name":"Cardiovascular Metabolic Research Janssen Pharmaceutical Companies of Johnson & Johnson San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da\u2010Thao","family":"Tran","sequence":"additional","affiliation":[{"name":"Cardiovascular Metabolic Research Janssen Pharmaceutical Companies of Johnson & Johnson San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hariharan","family":"Venkatesan","sequence":"additional","affiliation":[{"name":"Cardiovascular Metabolic Research Janssen Pharmaceutical Companies of Johnson & Johnson San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D","family":"Rosen","sequence":"additional","affiliation":[{"name":"Aetheria Therapeutics San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel 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