title: An o-aminoanilide analogue of 1α,25-dihydroxyvitamin D(3) functions as a strong vitamin D receptor antagonist.
abstract: Vitamin D receptor (VDR) antagonists have therapeutic potential in treatment of allergic conditions and hypercalcemia driven by granulomatous diseases. We have identified an o-aminoanilide analogue of the hormonal form of vitamin D with a dienyl side chain that functions as a strong VDR antagonist. Modeling studies indicate that antagonism arises from side chain rigidity, when compared to a more flexible saturated analogue, which interferes with H12 folding/alignment.
authors.affiliation: Departments of Chemistry, McGill University, Montreal, Quebec, H3A 2K6, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Lamblin
authors.forename: Russell
authors.initials: R
authors.lastname: Spingarn
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Wang
authors.forename: Melanie C
authors.initials: MC
authors.lastname: Burger
authors.forename: Basel
authors.initials: B
authors.lastname: Dabbas
authors.forename: Nicolas
authors.initials: N
authors.lastname: Moitessier
authors.forename: John H
authors.initials: JH
authors.lastname: White
authors.forename: James L
authors.initials: JL
authors.lastname: Gleason
mesh_terms: D000813:Anilides / Q000138:chemical synthesis* / Q000494:pharmacology; D001667:Binding, Competitive; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D005454:Fluorescence Polarization; D006801:Humans; D008958:Models, Molecular; D018167:Receptors, Calcitriol / Q000819:agonists / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013250:Steroid Hydroxylases / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D065668:Vitamin D3 24-Hydroxylase; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000813:Anilides; D016207:Cytokines; C553270:N-(2-aminophenyl)-6-(4-(2-(3,5-dihydroxycyclohexylidene)ethylidene)-7a-methyloctahydro-1H-inden-1-yl)-4-methylhepta-2,4-dienamide; D018167:Receptors, Calcitriol; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; D000094632:Thymic Stromal Lymphopoietin