Novel vitamin D analogs as potential therapeutics

Metabolism, toxicity profiling, and antiproliferative activity

Jianjun Chen, Jin Wang, Tae Kang Kim, Elaine W. Tieu, Edith K.Y. Tang, Zongtao Lin, Dianne Kovacic, Duane Miller, Arnold Postlethwaite, Robert C. Tuckey, Andrzej T. Slominski, Wei Li

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Aim: To discover novel [20(OH)D 3 ] analogs as antiproliferative therapeutics. Materials and Methods: We studied in vitro liver microsome stability, in vivo toxicity using mice, vitamin D receptor (VDR) translocation, in vitro antiproliferative effect, CYP enzyme metabolism. Results: 20S-And 20R(OH)D 3 had reasonable half-lives of 50 min and 30 min (average) respectively in liver microsomes. They were non-hypercalcemic at a high dose of 60 ìg/kg. Three new 20(OH)D 3 analogs were designed, synthesized and tested. They showed higher or comparable potency for inhibition of proliferation of normal keratinocytes and in the induction of VDR translocation from cytoplasm to nucleus, compared to 1,25(OH)2D 3 . These new analogs demonstrated different degrees of metabolism through a range of vitamin D-metabolizing CYP enzymes. Conclusion: Their lack of calcemic toxicity at high doses and their high biological activity suggest that this novel 20(OH)D 3 scaffold may represent a promising platform for further development of therapeutically-useful agents.

Original languageEnglish (US)
Pages (from-to)2153-2164
Number of pages12
JournalAnticancer research
Volume34
Issue number5
StatePublished - May 1 2014

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Calcitriol Receptors
Liver Microsomes
Vitamin D
Enzymes
Keratinocytes
Cytoplasm
Therapeutics
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Chen, J., Wang, J., Kim, T. K., Tieu, E. W., Tang, E. K. Y., Lin, Z., ... Li, W. (2014). Novel vitamin D analogs as potential therapeutics: Metabolism, toxicity profiling, and antiproliferative activity. Anticancer research, 34(5), 2153-2164.

Novel vitamin D analogs as potential therapeutics : Metabolism, toxicity profiling, and antiproliferative activity. / Chen, Jianjun; Wang, Jin; Kim, Tae Kang; Tieu, Elaine W.; Tang, Edith K.Y.; Lin, Zongtao; Kovacic, Dianne; Miller, Duane; Postlethwaite, Arnold; Tuckey, Robert C.; Slominski, Andrzej T.; Li, Wei.

In: Anticancer research, Vol. 34, No. 5, 01.05.2014, p. 2153-2164.

Research output: Contribution to journalArticle

Chen, J, Wang, J, Kim, TK, Tieu, EW, Tang, EKY, Lin, Z, Kovacic, D, Miller, D, Postlethwaite, A, Tuckey, RC, Slominski, AT & Li, W 2014, 'Novel vitamin D analogs as potential therapeutics: Metabolism, toxicity profiling, and antiproliferative activity', Anticancer research, vol. 34, no. 5, pp. 2153-2164.
Chen, Jianjun ; Wang, Jin ; Kim, Tae Kang ; Tieu, Elaine W. ; Tang, Edith K.Y. ; Lin, Zongtao ; Kovacic, Dianne ; Miller, Duane ; Postlethwaite, Arnold ; Tuckey, Robert C. ; Slominski, Andrzej T. ; Li, Wei. / Novel vitamin D analogs as potential therapeutics : Metabolism, toxicity profiling, and antiproliferative activity. In: Anticancer research. 2014 ; Vol. 34, No. 5. pp. 2153-2164.
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