{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:06:17Z","timestamp":1781712377970,"version":"3.54.5"},"reference-count":44,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106995\/Z\/15\/Z"],"award-info":[{"award-number":["106995\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2025,4]]},"DOI":"10.1016\/j.jbc.2025.108404","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T16:07:50Z","timestamp":1741795670000},"page":"108404","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"title":["Characterization of quinazolinone calcilytic therapy for autosomal dominant hypocalcemia type 1 (ADH1)"],"prefix":"10.1016","volume":"301","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2975-5170","authenticated-orcid":false,"given":"Fadil M.","family":"Hannan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9547-2067","authenticated-orcid":false,"given":"Kreepa G.","family":"Kooblall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8616-0205","authenticated-orcid":false,"given":"Mark","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7293-254X","authenticated-orcid":false,"given":"Taha","family":"Elajnaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0764-8681","authenticated-orcid":false,"given":"Kate E.","family":"Lines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3928-1001","authenticated-orcid":false,"given":"Xin","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward F.","family":"Nemeth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K.","family":"Shoichet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Kneissel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0106-364X","authenticated-orcid":false,"given":"Juerg A.","family":"Gasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1438-3220","authenticated-orcid":false,"given":"Rajesh V.","family":"Thakker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2025.108404_bib1","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1056\/NEJM199610103351505","article-title":"A\u00a0familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor","volume":"335","author":"Pearce","year":"1996","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.jbc.2025.108404_bib2","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1002\/jbmr.4659","article-title":"Autosomal dominant hypocalcemia type 1: a systematic review","volume":"37","author":"Roszko","year":"2022","journal-title":"J.\u00a0Bone Miner Res."},{"key":"10.1016\/j.jbc.2025.108404_bib3","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1056\/NEJMoa1300253","article-title":"Mutations affecting G-protein subunit alpha11 in hypercalcemia and hypocalcemia","volume":"368","author":"Nesbit","year":"2013","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.jbc.2025.108404_bib4","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1530\/EJE-16-0109","article-title":"Impaired growth and intracranial calcifications in autosomal dominant hypocalcemia caused by a GNA11 mutation","volume":"175","author":"Tenhola","year":"2016","journal-title":"Eur. J. Endocrinol."},{"key":"10.1016\/j.jbc.2025.108404_bib5","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1002\/jbmr.4803","article-title":"GNA11 variants identified in patients with hypercalcemia or hypocalcemia","volume":"38","author":"Howles","year":"2023","journal-title":"J.\u00a0Bone Miner Res."},{"key":"10.1016\/j.jbc.2025.108404_bib6","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41574-018-0115-0","article-title":"The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases","volume":"15","author":"Hannan","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.jbc.2025.108404_bib7","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.ajhg.2020.04.006","article-title":"Familial hypocalciuric hypercalcemia type 1 and autosomal-dominant hypocalcemia type 1: prevalence in a large healthcare population","volume":"106","author":"Dershem","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.jbc.2025.108404_bib8","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1111\/j.1365-2265.2011.04142.x","article-title":"Activating mutations in the calcium-sensing receptor: genetic and clinical spectrum in 25 patients with autosomal dominant hypocalcaemia - a German survey","volume":"75","author":"Raue","year":"2011","journal-title":"Clin. Endocrinol. (Oxf)"},{"key":"10.1016\/j.jbc.2025.108404_bib9","article-title":"Autosomal dominant hypocalcemia type 1 (ADH1) associated with myoclonus and intracerebral calcifications","volume":"6","author":"Elston","year":"2022","journal-title":"J.\u00a0Endocr. Soc."},{"key":"10.1016\/j.jbc.2025.108404_bib10","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1056\/NEJMc2034981","article-title":"PTH infusion for seizures in autosomal dominant hypocalcemia type 1","volume":"385","author":"Sastre","year":"2021","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.jbc.2025.108404_bib11","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1097\/01.ASN.0000025781.16723.68","article-title":"Functional characterization of a calcium-sensing receptor mutation in severe autosomal dominant hypocalcemia with a Bartter-like syndrome","volume":"13","author":"Vargas-Poussou","year":"2002","journal-title":"J.\u00a0Am. Soc. Nephrol."},{"key":"10.1016\/j.jbc.2025.108404_bib12","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S0140-6736(02)09842-2","article-title":"Association between activating mutations of calcium-sensing receptor and Bartter's syndrome","volume":"360","author":"Watanabe","year":"2002","journal-title":"Lancet"},{"key":"10.1016\/j.jbc.2025.108404_bib13","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.1111\/bph.14086","article-title":"Calcimimetic and calcilytic therapies for inherited disorders of the calcium-sensing receptor signalling pathway","volume":"175","author":"Hannan","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jbc.2025.108404_bib14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pmch.2017.12.001","article-title":"Discovery and development of calcimimetic and calcilytic compounds","volume":"57","author":"Nemeth","year":"2018","journal-title":"Prog. Med. Chem."},{"key":"10.1016\/j.jbc.2025.108404_bib15","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1210\/en.2017-00111","article-title":"Mutant mice with calcium-sensing receptor activation have hyperglycemia that is rectified by calcilytic therapy","volume":"158","author":"Babinsky","year":"2017","journal-title":"Endocrinology"},{"key":"10.1016\/j.jbc.2025.108404_bib16","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1002\/jbmr.2551","article-title":"Calcilytic ameliorates abnormalities of mutant calcium-sensing receptor (CaSR) knock-in mice mimicking autosomal dominant hypocalcemia (ADH)","volume":"30","author":"Dong","year":"2015","journal-title":"J.\u00a0Bone Miner Res."},{"key":"10.1016\/j.jbc.2025.108404_bib17","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0115178","article-title":"Amino alcohol- (NPS-2143) and quinazolinone-derived calcilytics (ATF936 and AXT914) differentially mitigate excessive signalling of calcium-sensing receptor mutants causing Bartter syndrome Type 5 and autosomal dominant hypocalcemia","volume":"9","author":"Letz","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.jbc.2025.108404_bib18","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1002\/jbmr.3747","article-title":"Treatment of autosomal dominant hypocalcemia type 1 with the calcilytic NPSP795 (SHP635)","volume":"34","author":"Roberts","year":"2019","journal-title":"J.\u00a0Bone Miner Res."},{"key":"10.1016\/j.jbc.2025.108404_bib19","doi-asserted-by":"crossref","DOI":"10.1002\/jbm4.10402","article-title":"Calcilytic NPSP795 increases plasma calcium and PTH in an autosomal dominant hypocalcemia type 1 mouse model","volume":"4","author":"Hannan","year":"2020","journal-title":"JBMR Plus"},{"key":"10.1016\/j.jbc.2025.108404_bib20","doi-asserted-by":"crossref","first-page":"3114","DOI":"10.1210\/en.2015-1269","article-title":"The calcilytic agent NPS 2143 rectifies hypocalcemia in a mouse model with an activating calcium-sensing receptor (CaSR) mutation: relevance to autosomal dominant hypocalcemia type 1 (ADH1","volume":"156","author":"Hannan","year":"2015","journal-title":"Endocrinology"},{"key":"10.1016\/j.jbc.2025.108404_bib21","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1056\/NEJMc2302708","article-title":"Efficacy and safety of encaleret in autosomal dominant hypocalcemia type 1","volume":"389","author":"Gafni","year":"2023","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.jbc.2025.108404_bib22","doi-asserted-by":"crossref","first-page":"21558","DOI":"10.1074\/jbc.M603682200","article-title":"A\u00a0missense mutation in the seven-transmembrane domain of the human Ca2+ receptor converts a negative allosteric modulator into a positive allosteric modulator","volume":"281","author":"Hu","year":"2006","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2025.108404_bib23","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1111\/bph.14961","article-title":"Negative allosteric modulators of the human calcium-sensing receptor bind to overlapping and distinct sites within the 7-transmembrane domain","volume":"177","author":"Josephs","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jbc.2025.108404_bib24","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41586-021-03691-0","article-title":"Asymmetric activation of the calcium-sensing receptor homodimer","volume":"595","author":"Gao","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2025.108404_bib25","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.bone.2014.04.015","article-title":"AXT914 a novel, orally-active parathyroid hormone-releasing drug in two early studies of healthy volunteers and postmenopausal women","volume":"64","author":"John","year":"2014","journal-title":"Bone"},{"key":"10.1016\/j.jbc.2025.108404_bib26","doi-asserted-by":"crossref","DOI":"10.1210\/endocr\/bqaa145","article-title":"A\u00a0new therapeutic approach using a calcilytic (AXT914) for postsurgical hypoparathyroidism in female rats","volume":"161","author":"Lim","year":"2020","journal-title":"Endocrinology"},{"key":"10.1016\/j.jbc.2025.108404_bib27","doi-asserted-by":"crossref","first-page":"13566","DOI":"10.1073\/pnas.0405516101","article-title":"Activating calcium-sensing receptor mutation in the mouse is associated with cataracts and ectopic calcification","volume":"101","author":"Hough","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"10.1016\/j.jbc.2025.108404_bib28","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1093\/jbmr\/zjae199","article-title":"An activating CaSR variant with biased signaling reveals a critical residue for Galpha11 coupling","volume":"40","author":"Benson","year":"2024","journal-title":"J.\u00a0Bone Miner Res."},{"key":"10.1016\/j.jbc.2025.108404_bib29","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2115849118","article-title":"Symmetric activation and modulation of the human calcium-sensing receptor","volume":"118","author":"Park","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"10.1016\/j.jbc.2025.108404_bib30","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.jbc.2025.108404_bib31","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.jbc.2025.108404_bib32","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1021\/acs.jmedchem.8b01855","article-title":"Fragment hits: what do they look like and how do they bind?","volume":"62","author":"Giordanetto","year":"2019","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.jbc.2025.108404_bib33","doi-asserted-by":"crossref","first-page":"9997","DOI":"10.1073\/pnas.96.18.9997","article-title":"The maximal affinity of ligands","volume":"96","author":"Kuntz","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"10.1016\/j.jbc.2025.108404_bib34","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1093\/hmg\/dds105","article-title":"Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites","volume":"21","author":"Hannan","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.jbc.2025.108404_bib35","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1007\/s00439-020-02199-3","article-title":"The Human Gene Mutation Database (HGMD((R))): optimizing its use in a clinical diagnostic or research setting","volume":"139","author":"Stenson","year":"2020","journal-title":"Hum. Genet."},{"key":"10.1016\/j.jbc.2025.108404_bib36","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1210\/en.2011-1426","article-title":"Positive and negative allosteric modulators promote biased signaling at the calcium-sensing receptor","volume":"153","author":"Davey","year":"2012","journal-title":"Endocrinology"},{"key":"10.1016\/j.jbc.2025.108404_bib37","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1124\/mol.119.118091","article-title":"Evaluation of operational models of agonism and allosterism at receptors with multiple orthosteric binding sites","volume":"97","author":"Gregory","year":"2020","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.jbc.2025.108404_bib38","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1021\/jm901811v","article-title":"1-Alkyl-4-phenyl-6-alkoxy-1H-quinazolin-2-ones: a novel series of potent calcium-sensing receptor antagonists","volume":"53","author":"Widler","year":"2010","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.jbc.2025.108404_bib39","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.aan3714","article-title":"A\u00a0calcium-sensing receptor mutation causing hypocalcemia disrupts a transmembrane salt bridge to activate beta-arrestin-biased signaling","volume":"11","author":"Gorvin","year":"2018","journal-title":"Sci. Signal"},{"key":"10.1016\/j.jbc.2025.108404_bib40","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1093\/hmg\/ddab076","article-title":"Ap2s1 mutation causes hypercalcaemia in mice and impairs interaction between calcium-sensing receptor and adaptor protein-2","volume":"30","author":"Hannan","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.jbc.2025.108404_bib41","doi-asserted-by":"crossref","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX: tools for structure building and analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci."},{"key":"10.1016\/j.jbc.2025.108404_bib42","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J.\u00a0Comput. Aided Mol. Des."},{"key":"10.1016\/j.jbc.2025.108404_bib43","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.jmb.2007.05.022","article-title":"Inference of macromolecular assemblies from crystalline state","volume":"372","author":"Krissinel","year":"2007","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.jbc.2025.108404_bib44","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1210\/en.2012-1887","article-title":"Impact of clinically relevant mutations on the pharmacoregulation and signaling bias of the calcium-sensing receptor by positive and negative allosteric modulators","volume":"154","author":"Leach","year":"2013","journal-title":"Endocrinology"}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925825002534?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925825002534?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T03:18:13Z","timestamp":1747106293000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925825002534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["S0021925825002534"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2025.108404","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Characterization of quinazolinone calcilytic therapy for autosomal dominant hypocalcemia type 1 (ADH1)","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2025.108404","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology\u00e9","name":"copyright","label":"Copyright"}],"article-number":"108404"}}