{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:50:55Z","timestamp":1792788655361,"version":"4.5.0"},"reference-count":86,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","funder":[{"name":"Universit\u00c3\u00a9 Paris-Saclay","award":["2023 Technics Project from the Health and Drug Science Graduate School"],"award-info":[{"award-number":["2023 Technics Project from the Health and Drug Science Graduate School"]}]},{"name":"Universit\u00c3\u00a9 Paris-Saclay","award":["AAP IDEX \u00e2\u20ac\u0153INNOVATION and ENTREPRENEURSHIP\u00e2\u20ac\u009d POC IN LABS 2021"],"award-info":[{"award-number":["AAP IDEX \u00e2\u20ac\u0153INNOVATION and ENTREPRENEURSHIP\u00e2\u20ac\u009d POC IN LABS 2021"]}]},{"name":"Commissariat \u00c3\u00a0l'\u00c3\u2030nergie Atomique et aux \u00c3\u2030nergies Alternatives","award":["CFR PhD Scholarship"],"award-info":[{"award-number":["CFR PhD Scholarship"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>MQ232, a disulfide-bond reticulated peptide derived from a natural snake toxin, was optimized as a new aquaretic drug candidate.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>MQ232 showed very low acute and chronic toxicity in rat and a biodistribution in mice strongly in favor of the kidney organs.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            MQ232 induced a sole aquaretic effect and demonstrated high\n                            <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                            activities on hyponatremia and polycystic kidney disease models.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Vaptans were developed at the end of the previous century as vasopressin type 2 receptor antagonists. Tolvaptan is the most prescribed vaptan for hyponatremia and autosomal dominant polycystic kidney disease (ADPKD). However, its use is not as widespread as it should be due to price issues, a narrow therapeutic window, and some side effects. With the aim of discovering new efficient and safer vasopressin type 2 receptor antagonists, we screened animal venoms and identified several peptide toxins. Among them, mambaquaretin 1 (MQ1) displayed unique biological properties in that regard that it was the starting point for the development of a potential drug candidate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Human T-cell assays and bioinformatics were used to mitigate MQ1 immunogenicity risk. MQ232 biodistribution in mice was performed by positron emission tomography. Pharmacodynamics, pharmacokinetics, and acute and chronic toxicity tests were performed on control rats. A rat experimental model of desmopressin-induced hyponatremia,\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      mice model of kidney cysts, and mice orthologous model of ADPKD were used to validate MQ232 efficacy in these pathologies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Three mutations were introduced in MQ1 to mitigate its immunogenicity risk. A fourth gain-of-function mutation was added to generate MQ232. MQ232's safety was demonstrated by a first toxic dose as high as 3000 nmol\/kg and a strong kidney organ selectivity by positron emission tomography imaging, while showing almost no interaction with the liver. MQ232's efficacy was first demonstrated with an effective dose of 3 nmol\/kg in a hyponatremic model and then in polycystic kidney models, on which MQ232 significantly reduced cyst growth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We demonstrated, using diverse translational techniques and minimizing animal use, MQ232's safety and efficacy in several rodent models of hyponatremia and ADPKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000000505","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T12:20:30Z","timestamp":1729081230000},"page":"181-192","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["A Snake Toxin Derivative for Treatment of Hyponatremia and Polycystic Kidney Diseases"],"prefix":"10.1681","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9597-2463","authenticated-orcid":false,"given":"Goran","family":"Stanajic-Petrovic","sequence":"first","affiliation":[{"name":"CEA, D\u00e9partement M\u00e9dicaments et Technologies pour la Sant\u00e9 (DMTS), Universit\u00e9 Paris Saclay, SIMoS, Gif-sur-Yvette, France"},{"name":"Universit\u00e9 Paris-Saclay, CEA, INSERM, CNRS, BioMaps, Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4717-3446","authenticated-orcid":false,"given":"Mathilde","family":"Keck","sequence":"additional","affiliation":[{"name":"CEA, D\u00e9partement M\u00e9dicaments et Technologies pour la Sant\u00e9 (DMTS), Universit\u00e9 Paris Saclay, SIMoS, Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Barbe","sequence":"additional","affiliation":[{"name":"CEA, D\u00e9partement M\u00e9dicaments et Technologies 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1880-7596","authenticated-orcid":false,"given":"Pierre","family":"Isnard","sequence":"additional","affiliation":[{"name":"Anatomie et Cytologie Pathologiques, CHU Necker-Enfants Malades, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-2141","authenticated-orcid":false,"given":"Jean-Paul","family":"Duong Van Huyen","sequence":"additional","affiliation":[{"name":"Anatomie et Cytologie Pathologiques, CHU Necker-Enfants Malades, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khawla","family":"Chmeis","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, CEA, INSERM, CNRS, BioMaps, Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9kou Siramakan","family":"Diarra","sequence":"additional","affiliation":[{"name":"Humana Biosciences, 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6886-8549","authenticated-orcid":false,"given":"Florence","family":"Castelli","sequence":"additional","affiliation":[{"name":"CEA, D\u00e9partement M\u00e9dicaments et Technologies pour la Sant\u00e9 (DMTS), Universit\u00e9 Paris Saclay, SIMoS, Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7781-7735","authenticated-orcid":false,"given":"Alain","family":"Pruvost","sequence":"additional","affiliation":[{"name":"CEA, D\u00e9partement M\u00e9dicaments et Technologies pour la Sant\u00e9 (DMTS), Universit\u00e9 Paris Saclay, SIMoS, Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5576-5366","authenticated-orcid":false,"given":"Philippe","family":"Robin","sequence":"additional","affiliation":[{"name":"CEA, D\u00e9partement M\u00e9dicaments et Technologies pour la Sant\u00e9 (DMTS), Universit\u00e9 Paris Saclay, SIMoS, Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7976-1811","authenticated-orcid":false,"given":"Pascal","family":"Kessler","sequence":"additional","affiliation":[{"name":"CEA, D\u00e9partement M\u00e9dicaments et Technologies pour la Sant\u00e9 (DMTS), Universit\u00e9 Paris Saclay, SIMoS, Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7667-0401","authenticated-orcid":false,"given":"Catherine","family":"Llorens-Cortes","sequence":"additional","affiliation":[{"name":"CEA, D\u00e9partement M\u00e9dicaments et 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