Discovery of a "Gatekeeper" Antagonist that Blocks Entry Pathway to Retinoid X Receptors (RXRs) without Allosteric Ligand Inhibition in Permissive RXR Heterodimers.

Allosteric Regulation Circular Dichroism Crystallography, X-Ray Dimerization Ligands Retinoid X Receptors / antagonists & inhibitors

Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
14 01 2021
Historique:
pubmed: 29 12 2020
medline: 9 3 2021
entrez: 28 12 2020
Statut: ppublish

Résumé

Retinoid X receptor (RXR) heterodimers such as PPAR/RXR, LXR/RXR, and FXR/RXR can be activated by RXR agonists alone and are therefore designated as permissive. Similarly, existing RXR antagonists show allosteric antagonism toward partner receptor agonists in these permissive RXR heterodimers. Here, we show 1-(3-(2-ethoxyethoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2-(trifluoromethyl)-1

Identifiants

DOI: 10.1021/acs.jmedchem.0c01354 PMID: 33356247
pubmed: 33356247
doi: 10.1021/acs.jmedchem.0c01354
doi:

Substances chimiques

Ligands 0
Retinoid X Receptors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

430-439

Auteurs

Masaki Watanabe (M)

Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1, Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.

Michiko Fujihara (M)

Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1, Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
AIBIOS Company. Ltd., Tri-Seven Roppongi 8F 7-7-7 Roppongi, Minato-ku, Tokyo 106-0032, Japan.

Tomoharu Motoyama (T)

Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.

Mayu Kawasaki (M)

Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.

Shoya Yamada (S)

Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1, Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
Research Fellowship Division, Japan Society for the Promotion of Science, Sumitomo-Ichibancho FS Bldg., 8 Ichibancho, Chiyoda-ku, Tokyo 102-8472, Japan.

Yuta Takamura (Y)

Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1, Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.

Sohei Ito (S)

Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
ORCID: 0000-0002-9937-3100

Makoto Makishima (M)

Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
ORCID: 0000-0002-4630-905X

Shogo Nakano (S)

Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
ORCID: 0000-0002-6614-7158

Hiroki Kakuta (H)

Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1, Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
ORCID: 0000-0002-3633-8121

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Classifications MeSH

questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Régulation allostérique › Discovery of a "Gatekeeper" Antagonist that...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Analyse spectrale › Dichroïsme circulaire › Discovery of a "Gatekeeper" Antagonist that...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Cristallographie aux rayons X › Discovery of a "Gatekeeper" Antagonist that...
questionsmedicales.fr › Métabolisme › Dimérisation › Discovery of a "Gatekeeper" Antagonist that...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Ligands › Discovery of a "Gatekeeper" Antagonist that...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Récepteurs à l'acide rétinoïque › Récepteurs X des rétinoïdes › Discovery of a "Gatekeeper" Antagonist that...