Previtamin D3 with a trans-fused decalin CD-ring has pronounced genomic activity

Lieve Verlinden, Annemieke Verstuyf, Christel Verboven, Guy Eelen, Camiel De Ranter, Ling Jie Gao, Yong Jun Chen, Ibrahim Murad, Mihwa Choi, Keiko Yamamoto, Sachiko Yamada, Dirk Van Haver, Maurits Vandewalle, Pierre J. De Clercq, Roger Bouillon

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Deletion of C19 in the structure of 1α,25-dihydroxyvitamin D 3 [1,25(OH)2D3] does not substantially alter the biological potency but prevents the conversion between the vitamin and the previtamin form. Hence, this modification allows the study of locked previtamin and vitamin forms. The locked 19-nor-1,25(OH)2-previtamin D 3 analog (19-nor-previtamin D) had a low biological activity and was a rather weak activator of the genomic signal transduction pathway. 19-Nor-trans-decalin-1,25(OH)2-vitamin D3 (19-nor-TD-vitamin D), characterized by the presence of a trans-fused decalin CD-ring system, was 10-fold more potent than the parent compound and was a potent activator of the genomic signal transduction pathway. Surprisingly, the previtamin, 19-nor-trans-decalin-1,25(OH)2-previtamin D3 (19-nor-TD-previtamin D), was as potent as 1,25(OH)2D3 in inhibiting cell proliferation and inducing cell differentiation and represents the first previtamin structure with pronounced vitamin D-like activity. Furthermore, this compound interacted as efficiently as 1,25(OH) 2D3 with the vitamin D receptor (VDR), retinoid X receptor (RXR), coactivators, and DNA, which illustrated its potent ability to activate the genomic signal transduction pathway. Analysis of the transactivation potency of 12 VDR point mutants after stimulation with 19-nor-TD-previtamin D revealed that this analog used the same contact points within the receptor as did 1,25(OH)2D3. This could be confirmed by modeling analysis of this compound in the ligand binding pocket of VDR. In conclusion, a previtamin D3 analog is presented with genomic activities equivalent to 1,25(OH)2D3.

Original languageEnglish (US)
Pages (from-to)35476-35482
Number of pages7
JournalJournal of Biological Chemistry
Issue number37
StatePublished - Sep 12 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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