{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:10:35Z","timestamp":1760058635098,"version":"build-2065373602"},"reference-count":76,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sanifit Therapeutics","award":["PI22\/00121"],"award-info":[{"award-number":["PI22\/00121"]}]},{"name":"CSL Group","award":["PI22\/00121"],"award-info":[{"award-number":["PI22\/00121"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI22\/00121"],"award-info":[{"award-number":["PI22\/00121"]}]},{"name":"\u2018Fondo de Investigaci\u00f3n para la Salud\u2019 (FIS)","award":["PI22\/00121"],"award-info":[{"award-number":["PI22\/00121"]}]},{"DOI":"10.13039\/501100004587","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["PI22\/00121"],"award-info":[{"award-number":["PI22\/00121"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Ectopic calcification is a pathological condition characterized by the mineralization of soft tissues due to the deposition of calcium phosphate crystals. Hexasodium fytate (CSL525, previously known as SNF472) is a crystallization inhibitor being developed for the treatment of ectopic calcification-related disorders. Our aim was to investigate CSL525 for the treatment of soft-tissue calcification disorders in animal models of pseudoxanthoma elasticum and calcinosis cutis. Methods: In a first study, abcc6-\/- zebrafish larvae were exposed to 1 mM CSL525 for 7 days or kept under the same conditions without CSL525, and spinal mineralization was quantified. In a second study, abcc6-\/- mice were administered subcutaneously with CSL525 at 15 mg\/kg thrice weekly for eight weeks. Vehicle-treated WT (C57BL\/6J) and abcc6-\/- mice served as controls, and muzzle skin calcification was quantified. In a third study, calcinosis cutis was induced in rats through subcutaneous administration of 0.15 mg FeCl3 at two sites in the thorax. Rats were administered either subcutaneous CSL525 (60 mg\/kg) or vehicle (0.9% NaCl), and calcium content was measured in the skin. Results: CSL525 significantly reduced the calcified area (~40%) in abcc6a-\/- zebrafish larvae. The abcc6-\/- mice receiving CSL525 showed a 57% inhibition of muzzle calcification compared to vehicle-treated abcc6-\/- mice. CSL525 inhibited skin calcification development by 60% in the calcinosis cutis rat model. Conclusions: CSL525 may prove beneficial not only in preventing the progression of cardiovascular calcification but also in treating other ectopic calcification conditions, including skin calcification associated with genetic disorders such as PXE.<\/jats:p>","DOI":"10.3390\/ph18040567","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T07:42:01Z","timestamp":1744616521000},"page":"567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hexasodium Fytate (SNF472 or CSL525) Inhibits Ectopic Calcification in Various Pseudoxanthoma Elasticum and Calcinosis Cutis Animal Models"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1924-7727","authenticated-orcid":false,"given":"Miguel D.","family":"Ferrer","sequence":"first","affiliation":[{"name":"Renal Lithiasis and Pathological Calcification Group (LiRCaP), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, 07122 Palma, Spain"},{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07010 Palma, Spain"},{"name":"Sanifit Therapeutics S.A., a company of CSL Vifor, 07121 Palma, Spain"},{"name":"Molecular Biology, Health Geography and One Health (MolONE), University of the Balearic Islands, 07122 Palma, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5023-6917","authenticated-orcid":false,"given":"Maria del Mar","family":"P\u00e9rez-Ferrer","sequence":"additional","affiliation":[{"name":"Renal Lithiasis and Pathological Calcification Group (LiRCaP), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, 07122 Palma, Spain"},{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07010 Palma, Spain"},{"name":"Sanifit Therapeutics S.A., a company of CSL Vifor, 07121 Palma, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8842-2827","authenticated-orcid":false,"given":"Marc","family":"Blasco","sequence":"additional","affiliation":[{"name":"Renal Lithiasis and Pathological Calcification Group (LiRCaP), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, 07122 Palma, Spain"},{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07010 Palma, Spain"},{"name":"Sanifit Therapeutics S.A., a company of CSL Vifor, 07121 Palma, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ida Joely","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, PXE International Center of Excellence in Research and Clinical Care, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8495-7103","authenticated-orcid":false,"given":"Qiaoli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, PXE International Center of Excellence in Research and Clinical Care, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4491-0332","authenticated-orcid":false,"given":"Olivier M.","family":"Vanakker","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium"},{"name":"International Network on Ectopic Calcification (INTEC), 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Dangreau","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Renal Lithiasis and Pathological Calcification Group (LiRCaP), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, 07122 Palma, Spain"},{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07010 Palma, Spain"},{"name":"Sanifit Therapeutics S.A., a company of CSL Vifor, 07121 Palma, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Malagraba","sequence":"additional","affiliation":[{"name":"Renal Lithiasis and Pathological Calcification Group (LiRCaP), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, 07122 Palma, Spain"},{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07010 Palma, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Firas","family":"Bassissi","sequence":"additional","affiliation":[{"name":"Sanifit Therapeutics S.A., a company of CSL Vifor, 07121 Palma, Spain"},{"name":"International Network on Ectopic Calcification (INTEC), 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2671-3386","authenticated-orcid":false,"given":"Joan","family":"Perell\u00f3","sequence":"additional","affiliation":[{"name":"Renal Lithiasis and Pathological Calcification Group (LiRCaP), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, 07122 Palma, Spain"},{"name":"Health Research Institute of the Balearic Islands (IdISBa), 07010 Palma, Spain"},{"name":"Sanifit Therapeutics S.A., a company of CSL Vifor, 07121 Palma, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Salcedo","sequence":"additional","affiliation":[{"name":"Sanifit Therapeutics S.A., a company of CSL Vifor, 07121 Palma, Spain"},{"name":"International Network on Ectopic Calcification (INTEC), 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1161\/CIRCRESAHA.110.234914","article-title":"Arterial Calcification in Chronic Kidney Disease: Key Roles for Calcium and Phosphate","volume":"109","author":"Shanahan","year":"2011","journal-title":"Circ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Villa-Bellosta, R. (2021). Vascular Calcification: Key Roles of Phosphate and Pyrophosphate. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413536"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1681\/ASN.V12102131","article-title":"Association of Elevated Serum PO4, Ca \u00d7 PO4 Product, and Parathyroid Hormone with Cardiac Mortality Risk in Chronic Hemodialysis Patients","volume":"12","author":"Ganesh","year":"2001","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"E10","DOI":"10.1161\/01.RES.87.7.e10","article-title":"Phosphate Regulation of Vascular Smooth Muscle Cell Calcification","volume":"87","author":"Jono","year":"2000","journal-title":"Circ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1161\/ATVBAHA.106.132266","article-title":"Characterization of Phosphate Transport in Rat Vascular Smooth Muscle Cells: Implications for Vascular Calcification","volume":"27","author":"Bogaert","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1525-139X.2007.00257.x","article-title":"Inhibitors of Calcification in Blood and Urine","volume":"20","author":"Schlieper","year":"2007","journal-title":"Semin. Dial."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Nagaset, H., and Woessner, J.F. (1999). Matrix Metalloproteinases. J. Biol. Chem., 274.","DOI":"10.1074\/jbc.274.31.21491"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/sj.ki.5002353","article-title":"Endochondral Bone Formation Is Involved in Media Calcification in Rats and in Men","volume":"72","author":"Neven","year":"2007","journal-title":"Kidney Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1161\/ATVBAHA.110.204834","article-title":"Chondrocyte Rather than Osteoblast Conversion of Vascular Cells Underlies Medial Calcification in Uremic Rats","volume":"30","author":"Neven","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1053\/j.ackd.2006.10.007","article-title":"Mechanisms of Vascular Calcification","volume":"14","author":"Giachelli","year":"2007","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.mehy.2016.07.005","article-title":"Hypothesis: Phytate Is an Important Unrecognised Nutrient and Potential Intravenous Drug for Preventing Vascular Calcification","volume":"94","author":"Joubert","year":"2016","journal-title":"Med. Hypotheses"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1093\/ndt\/gfq582","article-title":"Progression of Aortic Calcification Is Associated with Disorders of Mineral Metabolism and Mortality in Chronic Dialysis Patients","volume":"26","author":"Noordzij","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.jcmg.2010.08.018","article-title":"Progression of Coronary Artery Calcium Predicts All-Cause Mortality","volume":"3","author":"Budoff","year":"2010","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0272-6386(03)00372-X","article-title":"Cardiovascular Complications in Chronic Kidney Disease","volume":"41","author":"Sarnak","year":"2003","journal-title":"Am. J. Kidney Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1681\/ASN.2008070692","article-title":"Vascular Calcification: The Killer of Patients with Chronic Kidney Disease","volume":"20","author":"Mizobuchi","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1007\/s40620-020-00916-9","article-title":"Disorders in Bone-Mineral Parameters and the Risk of Death in Persons with Chronic Kidney Disease Stages 4 and 5: The PECERA Study","volume":"34","author":"Molina","year":"2021","journal-title":"J. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"113","DOI":"10.5582\/irdr.2015.01014","article-title":"Pseudoxanthoma Elasticum and Skin: Clinical Manifestations, Histopathology, Pathomechanism, Perspectives of Treatment","volume":"4","author":"Marconi","year":"2015","journal-title":"IRDR"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0738-081X(88)90003-X","article-title":"History","volume":"6","author":"Neidner","year":"1988","journal-title":"Clin. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/76109","article-title":"Mutations in ABCC6 Cause Pseudoxanthoma Elasticum","volume":"25","author":"Bergen","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6001","DOI":"10.1073\/pnas.100041297","article-title":"Pseudoxanthoma Elasticum: Mutations in the MRP6 Gene Encoding a Transmembrane ATP-Binding Cassette (ABC) Transporter","volume":"97","author":"Ringpfeil","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/76102","article-title":"Mutations in a Gene Encoding an ABC Transporter Cause Pseudoxanthoma Elasticum","volume":"25","author":"Saux","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.ajpath.2022.01.012","article-title":"Inorganic Pyrophosphate Deficiency Syndromes and Potential Treatments for Pathologic Tissue Calcification","volume":"192","author":"Ralph","year":"2022","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.matbio.2012.02.004","article-title":"Connective Tissue Mineralization in Abcc6\u2212\/\u2212 Mice, a Model for Pseudoxanthoma Elasticum","volume":"31","author":"Kavukcuoglu","year":"2012","journal-title":"Matrix Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1080\/14656566.2023.2266381","article-title":"Future Treatment of Vascular Calcification in Chronic Kidney Disease","volume":"24","author":"Cozzolino","year":"2023","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s11914-023-00782-x","article-title":"Impact of Cinacalcet and Etelcalcetide on Bone Mineral and Cardiovascular Disease in Dialysis Patients","volume":"21","author":"Bernardor","year":"2023","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"232","DOI":"10.2215\/CJN.06800615","article-title":"Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD: A Meta-Analysis of Randomized Controlled Trials","volume":"11","author":"Patel","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_27","first-page":"CD006023","article-title":"Phosphate Binders for Preventing and Treating Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)","volume":"2018","author":"Ruospo","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/nrneph.2009.99","article-title":"Sodium Thiosulfate in the Treatment of Calcific Uremic Arteriolopathy","volume":"5","author":"Schlieper","year":"2009","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1038\/ki.2008.455","article-title":"Sodium Thiosulfate Prevents Vascular Calcifications in Uremic Rats","volume":"74","author":"Pasch","year":"2008","journal-title":"Kidney Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1093\/ndt\/gfz204","article-title":"Sodium Thiosulphate and Progression of Vascular Calcification in End-Stage Renal Disease Patients: A Double-Blind, Randomized, Placebo-Controlled Study","volume":"35","author":"Djuric","year":"2020","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1097\/01.ASN.0000128955.83129.9C","article-title":"Phosphate-Induced Vascular Calcification: Role of Pyrophosphate and Osteopontin","volume":"15","author":"Lomashvili","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/ki.2010.461","article-title":"Treatment with Pyrophosphate Inhibits Uremic Vascular Calcification","volume":"79","author":"Lomashvili","year":"2011","journal-title":"Kidney Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.1093\/jn\/131.11.2910","article-title":"The Amino Bisphosphonate Ibandronate Prevents Vitamin D Toxicity and Inhibits Vitamin D-Induced Calcification of Arteries, Cartilage, Lungs and Kidneys in Rats","volume":"131","author":"Price","year":"2001","journal-title":"J. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/ki.2008.646","article-title":"Effect of Bisphosphonates on Vascular Calcification and Bone Metabolism in Experimental Renal Failure","volume":"75","author":"Lomashvili","year":"2009","journal-title":"Kidney Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1161\/01.ATV.21.5.817","article-title":"Bisphosphonates Alendronate and Ibandronate Inhibit Artery Calcification at Doses Comparable to Those That Inhibit Bone Resorption","volume":"21","author":"Price","year":"2001","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1080\/15384101.2015.1007809","article-title":"The Effects of Bisphosphonates on Ectopic Soft Tissue Mineralization Caused by Mutations in the ABCC6 Gene","volume":"14","author":"Li","year":"2015","journal-title":"Cell Cycle"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.15252\/emmm.201707532","article-title":"Oral Administration of Pyrophosphate Inhibits Connective Tissue Calcification","volume":"9","author":"Dedinszki","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/bjd.18632","article-title":"Severe Early-Onset Manifestations of Pseudoxanthoma Elasticum Resulting from the Cumulative Effects of Several Deleterious Mutations in ENPP1, ABCC6 and HBB: Transient Improvement in Ectopic Calcification with Sodium Thiosulfate","volume":"183","author":"Omarjee","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13063-024-08666-w","article-title":"The PROPHECI Trial: A Phase II, Double-Blind, Placebo-Controlled, Randomized Clinical Trial for the Treatment of Pseudoxanthoma Elasticum with Oral Pyrophosphate","volume":"26","author":"Clotaire","year":"2025","journal-title":"Trials"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s40620-019-00631-0","article-title":"Improvement in Wound Healing, Pain, and Quality of Life after 12 Weeks of SNF472 Treatment: A Phase 2 Open-Label Study of Patients with Calciphylaxis","volume":"32","author":"Brandenburg","year":"2019","journal-title":"J. Nephrol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4400","DOI":"10.1111\/bph.15163","article-title":"Mechanism of Action of SNF472, a Novel Calcification Inhibitor to Treat Vascular Calcification and Calciphylaxis","volume":"177","author":"Ferrer","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ferrer, M.D., Ketteler, M., Tur, F., Tur, E., Isern, B., Salcedo, C., Joubert, P.H., Behets, G.J., Neven, E., and D\u2019Haese, P.C. (2018). Characterization of SNF472 Pharmacokinetics and Efficacy in Uremic and Non-Uremic Rats Models of Cardiovascular Calcification. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197061"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1161\/CIRCULATIONAHA.119.044195","article-title":"Slowing Progression of Cardiovascular Calcification with SNF472 in Patients on Hemodialysis: Results of a Randomized Phase 2b Study","volume":"141","author":"Raggi","year":"2020","journal-title":"Circulation"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1097\/MNH.0000000000000726","article-title":"SNF472: Mechanism of Action and Results from Clinical Trials","volume":"30","author":"Sinha","year":"2021","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1007\/s40620-024-01909-8","article-title":"SNF472: A Novel Therapeutic Agent for Vascular Calcification and Calciphylaxis","volume":"37","author":"Yang","year":"2024","journal-title":"J. Nephrol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1681\/ASN.2021101327","article-title":"Interventions To Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials","volume":"33","author":"Xu","year":"2022","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1056\/NEJMra1505292","article-title":"Calciphylaxis","volume":"378","author":"Nigwekar","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"106583","DOI":"10.1016\/j.vph.2019.106583","article-title":"SNF472, a Novel Anti-Crystallization Agent, Inhibits Induced Calcification in an in Vitro Model of Human Aortic Valve Calcification","volume":"122\u2013123","author":"Zabirnyk","year":"2019","journal-title":"Vasc. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1161\/01.ATV.0000133194.94939.42","article-title":"Vascular Calcification: Mechanisms and Clinical Ramifications","volume":"24","author":"Abedin","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1161\/01.RES.0000161997.24797.c0","article-title":"Regulation of Vascular Calcification: Roles of Phosphate and Osteopontin","volume":"96","author":"Giachelli","year":"2005","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1002\/jbmr.93","article-title":"High-Phosphate-Induced Calcification Is Related to SM22\u03b1 Promoter Methylation in Vascular Smooth Muscle Cells","volume":"25","author":"Oca","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"C210","DOI":"10.1152\/ajpcell.00229.2010","article-title":"Role of Calcium-Phosphate Deposition in Vascular Smooth Muscle Cell Calcification","volume":"300","author":"Millan","year":"2011","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1111\/j.1523-1755.2004.66015.x","article-title":"Elevated Extracellular Calcium Levels Induce Smooth Muscle Cell Matrix Mineralization in Vitro","volume":"66","author":"Yang","year":"2004","journal-title":"Kidney Int."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wynsberghe, J.V., and Vanakker, O.M. (2023). Significance of Premature Vertebral Mineralization in Zebrafish Models in Mechanistic and Pharmaceutical Research on Hereditary Multisystem Diseases. Biomolecules, 13.","DOI":"10.3390\/biom13111621"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Gils, M.V., Willaert, A., Coucke, P.J., and Vanakker, O.M. (2022). The Abcc6a Knockout Zebrafish Model as a Novel Tool for Drug Screening for Pseudoxanthoma Elasticum. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.822143"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1242\/dev.113811","article-title":"Vitamin K Reduces Hypermineralisation in Zebrafish Models of PXE and GACI","volume":"142","author":"Mackay","year":"2015","journal-title":"Development"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1016\/j.jid.2021.10.019","article-title":"Minocycline Attenuates Excessive DNA Damage Response and Reduces Ectopic Calcification in Pseudoxanthoma Elasticum","volume":"142","author":"Nollet","year":"2022","journal-title":"J. Investig. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1111\/exd.14636","article-title":"ABCC6 Deficiency and Bone Loss: A Double Benefit of Etidronate for Patient Presenting with Pseudoxanthoma Elasticum?","volume":"31","author":"Kauffenstein","year":"2022","journal-title":"Exp. Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Perez, M.M., Ferrer, M.D., Lazo-Rodriguez, M., Canals, A.Z., Banon-Maneus, E., Campistol, J.M., Miller, S., Garg, R., Gold, A., and Salcedo, C. (2020). A Novel Assay to Measure Calcification Propensity: From Laboratory to Humans. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-74592-x"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Zabirnyk, A., Perez, M.D.M., Blasco, M., Stensl\u00f8kken, K.-O., Ferrer, M.D., Salcedo, C., and Vaage, J. (2020). A Novel Ex Vivo Model of Aortic Valve Calcification. A Preliminary Report. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.568764"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8299","DOI":"10.1128\/MCB.25.18.8299-8310.2005","article-title":"Targeted Ablation of the Abcc6 Gene Results in Ectopic Mineralization of Connective Tissues","volume":"25","author":"Klement","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1111\/exd.14587","article-title":"INZ-701, a Recombinant ENPP1 Enzyme, Prevents Ectopic Calcification in an Abcc6\u2212\/\u2212 Mouse Model of Pseudoxanthoma Elasticum","volume":"31","author":"Jacobs","year":"2022","journal-title":"Exp. Dermatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1016\/j.ymthe.2024.09.028","article-title":"Novel Treatment for PXE: Recombinant ENPP1 Enzyme Therapy","volume":"32","author":"Jacobs","year":"2024","journal-title":"Mol. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.jid.2018.07.030","article-title":"Inhibition of Tissue-Nonspecific Alkaline Phosphatase Attenuates Ectopic Mineralization in the Abcc6\u2013\/\u2013 Mouse Model of PXE but Not in the Enpp1 Mutant Mouse Models of GACI","volume":"139","author":"Li","year":"2019","journal-title":"J. Investig. Dermatol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bouderlique, E., Nollet, L., Letavernier, E., and Vanakker, O.M. (2022). Minocycline Counteracts Ectopic Calcification in a Murine Model of Pseudoxanthoma Elasticum: A Proof-of-Concept Study. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031838"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1111\/exd.14288","article-title":"A Phytic Acid Analogue INS-3001 Prevents Ectopic Calcification in an Abcc6-\/-; Mouse Model of Pseudoxanthoma Elasticum","volume":"30","author":"Jacobs","year":"2021","journal-title":"Exp. Dermatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/s41467-019-14091-4","article-title":"Inhibition of Vascular Calcification by Inositol Phosphates Derivatized with Ethylene Glycol Oligomers","volume":"11","author":"Schantl","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"736","DOI":"10.2215\/CJN.16931020","article-title":"Effects of Myo-Inositol Hexaphosphate (SNF472) on Bone Mineral Density in Patients Receiving Hemodialysis: An Analysis of the Randomized, Placebo-Controlled CaLIPSO Study","volume":"16","author":"Bushinsky","year":"2021","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s00223-002-1006-9","article-title":"The Amino Bisphosphonate Ibandronate Prevents Calciphylaxis in the Rat at Doses That Inhibit Bone Resorption","volume":"71","author":"Price","year":"2002","journal-title":"Calcif. Tissue Int."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1111\/j.1365-2133.2005.06382.x","article-title":"Study of a Myo-Inositol Hexaphosphate-Based Cream to Prevent Dystrophic Calcinosis Cutis","volume":"152","author":"Grases","year":"2005","journal-title":"Br. J. Dermatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"115392","DOI":"10.1016\/j.bone.2020.115392","article-title":"Pharmacological TNAP Inhibition Efficiently Inhibits Arterial Media Calcification in a Warfarin Rat Model but Deserves Careful Consideration of Potential Physiological Bone Formation\/Mineralization Impairment","volume":"137","author":"Opdebeeck","year":"2020","journal-title":"Bone"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1016\/j.jid.2018.06.183","article-title":"Generation and Validation of a Complete Knockout Model of Abcc6a in Zebrafish","volume":"138","author":"Gils","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1016\/j.jid.2022.01.022","article-title":"Inhibition of the DNA Damage Response Attenuates Ectopic Calcification in Pseudoxanthoma Elasticum","volume":"142","author":"Huang","year":"2022","journal-title":"J. Investig. Dermatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.gim.2021.08.011","article-title":"Genetic Heterogeneity of Heritable Ectopic Mineralization Disorders in a Large International Cohort","volume":"24","author":"Saeidian","year":"2022","journal-title":"Genet. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jchromb.2013.03.023","article-title":"Validation of an LC-MS Bioanalytical Method for Quantification of Phytate Levels in Rat, Dog and Human Plasma","volume":"928","author":"Tur","year":"2013","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/4\/567\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:13:57Z","timestamp":1760030037000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/4\/567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,14]]},"references-count":76,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ph18040567"],"URL":"https:\/\/doi.org\/10.3390\/ph18040567","relation":{},"ISSN":["1424-8247"],"issn-type":[{"type":"electronic","value":"1424-8247"}],"subject":[],"published":{"date-parts":[[2025,4,14]]}}}