{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:03:18Z","timestamp":1792231398540,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,11,28]],"date-time":"2017-11-28T00:00:00Z","timestamp":1511827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","award":["Lilly Research Laboratories"],"award-info":[{"award-number":["Lilly Research Laboratories"]}],"id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["Intramural Research Program"],"award-info":[{"award-number":["Intramural Research Program"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Human parathyroid hormone (PTH) is critical for maintaining physiological calcium homeostasis and plays an important role in the formation and maintenance of the bone. Full\u2010length PTH and a truncated peptide form are approved for treatment of hypoparathyroidism and osteoporosis respectively. Our initial goal was to develop an improved PTH therapy for osteoporosis, but clinical development was halted. The novel compound was then repurposed as an improved therapy for hypoparathyroidism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>A longer\u2010acting form of PTH was synthesised by altering the peptide to increase cell surface residence time of the bound ligand to its receptor. <jats:italic>In vitro<\/jats:italic> screening identified a compound, which was tested in an animal model of osteoporosis before entering human trials. This compound was subsequently tested in two independent animal models of hypoparathyroidism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The peptide identified, LY627\u20102K, exhibited delayed internalization kinetics. In an ovariectomy\u2010induced bone loss rat model, LY627\u20102K demonstrated improved vertebral bone mineral density and biomechanical properties at skeletal sites and a modest increase in serum calcium. In a Phase I clinical study, dose\u2010dependent increases in serum calcium were reproduced. These observations prompted us to explore a second indication, hypoparathyroidism. In animal models of this disease, LY627\u20102K restored serum calcium, comparing favourably to treatment with wild\u2010type PTH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>We summarize the repositioning of a therapeutic candidate with substantial preclinical and clinical data. Our results support its repurposing and continued development, from a common indication (osteoporosis) to a rare disease (hypoparathyroidism) by exploiting a shared molecular target.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.2\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.2\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14028","type":"journal-article","created":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T21:52:38Z","timestamp":1505253158000},"page":"262-271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Repurposing a novel parathyroid hormone analogue to treat hypoparathyroidism"],"prefix":"10.1111","volume":"175","author":[{"given":"Venkatesh","family":"Krishnan","sequence":"first","affiliation":[{"name":"Musculoskeletal Research, Lilly Research Laboratories Eli Lilly and Company  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfei L","family":"Ma","sequence":"additional","affiliation":[{"name":"Musculoskeletal Research, Lilly Research Laboratories Eli Lilly and Company  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine Z","family":"Chen","sequence":"additional","affiliation":[{"name":"Therapeutics for Rare and Neglected Diseases (TRND) National Center for Advancing Translational Sciences (NCATS), NIH  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Thorne","sequence":"additional","affiliation":[{"name":"Therapeutics for Rare and Neglected Diseases (TRND) National Center for Advancing Translational Sciences (NCATS), NIH  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Bullock","sequence":"additional","affiliation":[{"name":"Musculoskeletal Research, Lilly Research Laboratories Eli Lilly and Company  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Tawa","sequence":"additional","affiliation":[{"name":"Therapeutics for Rare and Neglected Diseases (TRND) National Center for Advancing Translational Sciences (NCATS), NIH  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Javella\u2010Cauley","sequence":"additional","affiliation":[{"name":"Musculoskeletal Research, Lilly Research Laboratories Eli Lilly and Company  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyou","family":"Chu","sequence":"additional","affiliation":[{"name":"Lead Optimization Biology, Lilly Research Laboratories Eli Lilly and Company  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Li","sequence":"additional","affiliation":[{"name":"Lead Optimization Biology, Lilly Research Laboratories Eli Lilly and Company  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne","family":"Kohn","sequence":"additional","affiliation":[{"name":"Biotechnology Discovery Research, Lilly Research Laboratories Eli Lilly and Company  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary D","family":"Adrian","sequence":"additional","affiliation":[{"name":"Musculoskeletal Research, Lilly Research Laboratories Eli Lilly and Company  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Benson","sequence":"additional","affiliation":[{"name":"Musculoskeletal Research, Lilly Research Laboratories Eli Lilly and Company  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifei","family":"Liu","sequence":"additional","affiliation":[{"name":"Lead Optimization Biology, Lilly Research Laboratories Eli Lilly and Company  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Sato","sequence":"additional","affiliation":[{"name":"Musculoskeletal Research, Lilly Research Laboratories Eli Lilly and Company  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1034-0757","authenticated-orcid":false,"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Therapeutics for Rare and Neglected Diseases (TRND) National Center for Advancing Translational Sciences (NCATS), NIH  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-9095","authenticated-orcid":false,"given":"Andre M","family":"Pilon","sequence":"additional","affiliation":[{"name":"Therapeutics for Rare and Neglected Diseases (TRND) National Center for Advancing Translational Sciences (NCATS), NIH  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. 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