title: Altered activity profile of a tertiary silanol analog of multi-targeting nuclear receptor modulator T0901317.
abstract: We report the design, synthesis, and physicochemical/biological evaluation of novel silanol derivative 6 (sila-T) as a silanol analog of multi-target nuclear receptor modulator T0901317 (5). Compound 6 showed intermediate hydrophobicity between the corresponding alcohol 13 and perfluoroalcohol 5. While 5 exhibited potent activities toward liver X receptor α and β, farnesoid X receptor, pregnane X receptor (PXR) and retinoic acid receptor-related orphan receptor (ROR)γ, silanol 6 exhibited activity only toward PXR and RORs. Incorporation of silanol instead of perfluoroalcohol is a promising option for developing novel target-selective, biologically active compounds.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, 113-0032 Tokyo, Japan.
authors.forename: Hirozumi
authors.initials: H
authors.lastname: Toyama
authors.affiliation: Department of Biological Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Sato
authors.affiliation: Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shirakawa
authors.affiliation: Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Komai
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, 113-0032 Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, 113-0032 Tokyo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Fujii
mesh_terms: D018360:Crystallography, X-Ray; D057809:HEK293 Cells; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry* / Q000494:pharmacology*; D000071518:Liver X Receptors; D008958:Models, Molecular; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism*; D012821:Silanes / Q000737:chemistry* / Q000494:pharmacology*; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*; D000099150:Receptor, Farnesoid X-Activated; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D057093:Orphan Nuclear Receptors; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D012821:Silanes; D013449:Sulfonamides; D000099150:Receptor, Farnesoid X-Activated; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C082343:silanol
keywords: Nuclear receptor; Pregnane X receptor (PXR); Retinoic acid receptor-related orphan receptor (ROR); Sila-substitution; Silanol; T0901317