Discovery of biaryls as RORγ inverse agonists by using structure-based design

Autor:	Justin A. Caravella, Daliya Banerjee, Noel A. Powell, Jason D. Fontenot, Andres McKenzie, Istvan J. Enyedy, Victor Sukbong Hong, Douglas Marcotte, Laura Silvian, Jianhua Chao, Kurt Van Vloten
Rok vydání:	2016
Předmět:	Models Molecular 0301 basic medicine Hydrocarbons Fluorinated Lymphocyte Clinical Biochemistry Pharmaceutical Science Arthritis Inflammation Computational biology Biology Crystallography X-Ray Biochemistry Structure-Activity Relationship 03 medical and health sciences Psoriasis Drug Discovery Gene expression medicine Inverse agonist Structure–activity relationship Molecular Biology Sulfonamides Binding Sites Molecular Structure Organic Chemistry Innate lymphoid cell Nuclear Receptor Subfamily 1 Group F Member 3 medicine.disease Molecular Docking Simulation 030104 developmental biology medicine.anatomical_structure Drug Design Immunology Molecular Medicine medicine.symptom
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 26:2459-2463
ISSN:	0960-894X
Popis:	RORγ plays a critical role in controlling a pro-inflammatory gene expression program in several lymphocyte lineages including T cells, γδ T cells, and innate lymphoid cells. RORγ-mediated inflammation has been linked to susceptibility to Crohn's disease, arthritis, and psoriasis. Thus inverse agonists of RORγ have the potential of modulating inflammation. Our goal was to optimize two RORγ inverse agonists: T0901317 from literature and 1 that we obtained from internal screening. We used information from internal X-ray structures to design two libraries that led to a new biaryl series.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3136b750dc7319912bb39e7e65933a62 https://doi.org/10.1016/j.bmcl.2016.03.109 Zobrazit plný text záznamu Full Text from ScienceDirect