Potent, selective and low-calcemic inhibitors of CYP24 Hydroxylase: 24-Sulfoximine analogues of the hormone 1α,25-dihydroxyvitamin D 3

Mehmet Kahraman, Sandra Sinishtaj, Patrick M. Dolan, Thomas W. Kensler, Sara Peleg, Uttam Saha, Samuel S. Chuang, Galina Bernstein, Bozena Korczak, Gary H. Posner

Research output: Contribution to journalArticlepeer-review

Abstract

A dozen 24-sulfoximine analogues of the hormone 1α,25- dihydroxyvitamin D3 were prepared, differing not only at the stereogenic sulfoximine stereocenter but also at the A-ring. Although these sulfoximines were not active transcriptionally and were only very weakly antiproliferative, some of them are powerful hydroxylase enzyme inhibitors. Specifically, 24-(S)-NH phenyl sulfoximine 3a is an extremely potent CYP24 inhibitor (IC50 = 7.4 nM) having low calcemic activity. In addition, this compound shows high selectivity toward the CYP24 enzyme in comparison to CYP27A1 (IC50 > 1000 nM) and CYP27B (IC50 = 554 nM).

Original languageEnglish (US)
Pages (from-to)6854-6863
Number of pages10
JournalJournal of medicinal chemistry
Volume47
Issue number27
DOIs
StatePublished - Dec 30 2004

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'Potent, selective and low-calcemic inhibitors of CYP24 Hydroxylase: 24-Sulfoximine analogues of the hormone 1α,25-dihydroxyvitamin D <sub>3</sub>'. Together they form a unique fingerprint.

Cite this