مورد إلكتروني
Elucidation of an allosteric Mode of Action for a Thienopyrazole RORγt Inverse Agonist
| العنوان: | Elucidation of an allosteric Mode of Action for a Thienopyrazole RORγt Inverse Agonist |
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| المصدر: | ChemMedChem vol.15 (2020) date: 2020-04-03 nr.7 p.561-565 [ISSN 1860-7179] |
| بيانات النشر: | 2020 |
| تفاصيل مُضافة: | de Vries, Rens M.J.M. de Vries, Rens M.J.M. Doveston, Richard G. Meijer, Femke A. Brunsveld, Luc |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | The demand for allosteric targeting of nuclear receptors is high, but examples are limited, and structural information is scarce. The retinoic acid‐related orphan receptor gamma t (RORγt) is an important transcriptional regulator for the differentiation of T helper 17 cells for which the first, and some of the most promising, examples of allosteric nuclear receptor modulation have been reported and structurally proven. In a 2015 patent, filed by the pharmaceutical company Glenmark, a new class of small molecules was reported that act as potent inverse agonists for RORγt. A compound library around the central thienopyrazole scaffold captured a clear structure‐activity relationship, but the binding mechanism of this new class of RORγt modulators has not been elucidated. Using a combination of biochemical and X‐ray crystallography studies, here the allosteric mechanism for the inverse agonism for the most potent compound, classified in the patent as “example 13”, is reported, providing a strongly desired additional example of allosteric nuclear receptor targeting. |
| مصطلحات الفهرس: | Nuclear Receptors, RORγt, Allosteric Modulators, Structure Elucidation, Drug Discovery, ROR gamma t, Tijdschriftartikel, Article |
| URL: | |
| الإتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess |
| ملاحظة: | DOI: 10.1002/cmdc.202000044 ChemMedChem vol.15 (2020) date: 2020-04-03 nr.7 p.561-565 [ISSN 1860-7179] English |
| أرقام أخرى: | NLTUR oai:pure.tue.nl:publications/0bf721e3-eff7-43da-9dfb-10538bae9ae5 https://research.tue.nl/en/publications/0bf721e3-eff7-43da-9dfb-10538bae9ae5Test 1150882142 |
| المصدر المساهم: | TU/E REPOSITORY From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1150882142 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |