{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:28:51Z","timestamp":1780374531816,"version":"3.54.1"},"reference-count":83,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,31]],"date-time":"2021-10-31T00:00:00Z","timestamp":1635638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We have developed an in vitro system to easily examine the affinity for vitamin D receptor (VDR) and CYP24A1-mediated metabolism as two methods of assessing vitamin D derivatives. Vitamin D derivatives with high VDR affinity and resistance to CYP24A1-mediated metabolism could be good therapeutic agents. This system can effectively select vitamin D derivatives with these useful properties. We have also developed an in vivo system including a Cyp27b1-gene-deficient rat (a type I rickets model), a Vdr-gene-deficient rat (a type II rickets model), and a rat with a mutant Vdr (R270L) (another type II rickets model) using a genome editing method. For Cyp27b1-gene-deficient and Vdr mutant (R270L) rats, amelioration of rickets symptoms can be used as an index of the efficacy of vitamin D derivatives. Vdr-gene-deficient rats can be used to assess the activities of vitamin D derivatives specialized for actions not mediated by VDR. One of our original vitamin D derivatives, which displays high affinity VDR binding and resistance to CYP24A1-dependent metabolism, has shown good therapeutic effects in Vdr (R270L) rats, although further analysis is needed.<\/jats:p>","DOI":"10.3390\/ijms222111839","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:21:34Z","timestamp":1635805294000},"page":"11839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Development of In Vitro and In Vivo Evaluation Systems for Vitamin D Derivatives and Their Application to Drug Discovery"],"prefix":"10.3390","volume":"22","author":[{"given":"Kaori","family":"Yasuda","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyu","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Mano","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Takano","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo 173-8605, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3091-2476","authenticated-orcid":false,"given":"Atsushi","family":"Kittaka","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo 173-8605, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5311-4069","authenticated-orcid":false,"given":"Shinichi","family":"Ikushiro","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Sakaki","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,31]]},"reference":[{"key":"ref_1","first-page":"195","article-title":"Phase II trial of oral 1,25-dihydroxyvitamin D (calcitriol) in hormone refractory prostate cancer","volume":"1","author":"Osborn","year":"1995","journal-title":"Urol. 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