{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:28:43Z","timestamp":1792636123850,"version":"4.5.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of symptomatic biliary cysts. Current surgical and pharmacological approaches are ineffective, and liver transplantation represents the only curative option. Ursodeoxycholic acid (UDCA) and histone deacetylase 6 inhibitors (HDAC6is) have arisen as promising therapeutic strategies, but with partial benefits.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Here, we tested an approach based on the design, synthesis, and validation of a family of UDCA synthetic conjugates with selective HDAC6i capacity (UDCA\u2010HDAC6i). Four UDCA\u2010HDAC6i conjugates presented selective HDAC6i activity, UDCA\u2010HDAC6i #1 being the most promising candidate. UDCA orientation within the UDCA\u2010HDAC6i structure was determinant for HDAC6i activity and selectivity. Treatment of polycystic rats with UDCA\u2010HDAC6i #1 reduced their hepatomegaly and cystogenesis, increased UDCA concentration, and inhibited HDAC6 activity in liver. In cystic cholangiocytes UDCA\u2010HDAC6i #1 restored primary cilium length and exhibited potent antiproliferative activity. UDCA\u2010HDAC6i #1 was actively transported into cells through BA and organic cation transporters.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These UDCA\u2010HDAC6i conjugates open a therapeutic avenue for PLDs.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31216","type":"journal-article","created":{"date-parts":[[2020,3,7]],"date-time":"2020-03-07T16:21:36Z","timestamp":1583598096000},"page":"186-203","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Synthetic Conjugates of Ursodeoxycholic Acid Inhibit Cystogenesis in Experimental Models of Polycystic Liver Disease"],"prefix":"10.1097","volume":"73","author":[{"given":"Francisco J.","family":"Caballero\u2010Camino","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry I,Center of Innovation in Advanced Chemistry (ORFEO\u2010CINQA),University of the Basque Country\/Euskal Herriko Unibertsitatea (UPV\/EHU),Donostia International Physics Center (DIPC),Donostia\u2010San Sebastian,Spain"},{"name":"Department of Liver and Gastrointestinal Diseases,Biodonostia Health Research Institute,Donostia University Hospital,UPV\/EHU,Donostia\u2010San Sebastian,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1984-7183","authenticated-orcid":false,"given":"Ivan","family":"Rivilla","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry I,Center of Innovation in Advanced Chemistry (ORFEO\u2010CINQA),University of the Basque Country\/Euskal Herriko Unibertsitatea (UPV\/EHU),Donostia International Physics Center (DIPC),Donostia\u2010San 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