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Structural Modification of the Natural Product Valerenic Acid Tunes RXR Homodimer Agonism.

التفاصيل البيبلوغرافية
العنوان: Structural Modification of the Natural Product Valerenic Acid Tunes RXR Homodimer Agonism.
المؤلفون: Zaienne D; Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt, Germany., Isigkeit L; Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt, Germany., Marschner JA; Department of Pharmacy, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377, Munich, Germany., Duensing-Kropp S; Department of Pharmacy, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377, Munich, Germany., Höfner G; Department of Pharmacy, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377, Munich, Germany., Merk D; Department of Pharmacy, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377, Munich, Germany.; Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt, Germany.
المصدر: ChemMedChem [ChemMedChem] 2023 Nov 02; Vol. 18 (21), pp. e202300404. Date of Electronic Publication: 2023 Sep 25.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 101259013 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1860-7187 (Electronic) Linking ISSN: 18607179 NLM ISO Abbreviation: ChemMedChem Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Weinheim, Germany : Wiley-VCH, c2006-
مواضيع طبية MeSH: Sesquiterpenes* , Indenes*/pharmacology, Retinoid X Receptors/metabolism ; Receptors, Cytoplasmic and Nuclear
مستخلص: Retinoid X receptors (RXR) are ligand-sensing transcription factors with a unique role in nuclear receptor signaling as universal heterodimer partners. RXR modulation holds potential in cancer, neurodegeneration and metabolic diseases but adverse effects of RXR activation and lack of selective modulators prevent further exploration as therapeutic target. The natural product valerenic acid has been discovered as RXR agonist with unprecedented preference for RXR subtype and homodimer activation. To capture structural determinants of this activity profile and identify potential for optimization, we have studied effects of structural modification of the natural product on RXR modulation and identified an analogue with enhanced RXR homodimer agonism.
(© 2023 The Authors. ChemMedChem published by Wiley-VCH GmbH.)
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معلومات مُعتمدة: ME 5481/1-1 German Research Foundation
فهرسة مساهمة: Keywords: cancer; natural product synthesis; neurodegeneration; retinoid X receptor; transcription factor
المشرفين على المادة: 34NDB285PM (valerenic acid)
0 (Sesquiterpenes)
0 (Indenes)
0 (Retinoid X Receptors)
0 (Receptors, Cytoplasmic and Nuclear)
تواريخ الأحداث: Date Created: 20230912 Date Completed: 20231110 Latest Revision: 20240326
رمز التحديث: 20240326
DOI: 10.1002/cmdc.202300404
PMID: 37697963
قاعدة البيانات: MEDLINE
الوصف
تدمد:1860-7187
DOI:10.1002/cmdc.202300404