Craig C. Correll

Discovery of N-(Indazol-3-yl)piperidine-4-carboxylic Acids as RORγt Allosteric Inhibitors for Autoimmune Diseases

Hongjun Zhang, Blair T. Lapointe, Neville J. Anthony, Rita Azevedo et autres

The clinical success of anti-IL-17 monoclonal antibodies (i.e., Cosentyx and Taltz) has validated Th17 pathway modulation for the treatment of autoimmune diseases. The nuclear hormone receptor RORγt is a master regulator of Th17 cells and affects the production of a host of …

us, nl (code pays fourni par la source)

Discovery of MK-8318, a Potent and Selective CRTh2 Receptor Antagonist for the Treatment of Asthma

Xianhai Huang, Jason D. Brubaker, Wei Zhou, Purakkattle Biju et autres

A novel series of tricyclic tetrahydroquinolines were identified as potent and selective CRTh2 receptor antagonists. The agonism and antagonism switch was achieved through structure-based drug design (SBDD) using a CRTh2 receptor homologue model. The challenge of very low exposures in pharmacokinetic studies …

us (code pays fourni par la source)

The synthesis of 2,3,6-trisubstituted 1-oxo-1,2-dihydroisoquinolines as potent CRTh2 antagonists

Xianhai Huang, Ashwin U. Rao, Wei Zhou, Robert G. Aslanian et autres

us (code pays fourni par la source)

Inhibition of RORγT Skews TCRα Gene Rearrangement and Limits T Cell Repertoire Diversity

Yanxia Guo, Kenzie D. MacIsaac, Yi Chen, Richard J. Miller et autres

Recent studies have elucidated the molecular mechanism of RORγT transcriptional regulation of Th17 differentiation and function. RORγT was initially identified as a transcription factor required for thymopoiesis by maintaining survival of CD4 + CD8 + (DP) thymocytes. While RORγ antagonists are currently …

us, sa (code pays fourni par la source)

Identification of an allosteric binding site for RORγt inhibition

Marcel Scheepstra, S. Leysen, Geert C. van Almen, J. Richard Miller et autres

RORγt is critical for the differentiation and proliferation of Th17 cells associated with several chronic autoimmune diseases. We report the discovery of a novel allosteric binding site on the nuclear receptor RORγt. Co-crystallization of the ligand binding domain (LBD) of RORγt with …

nl, us (code pays fourni par la source)

RORγt inhibitors suppress TH17 responses in inflammatory arthritis and inflammatory bowel disease

Jelle de Wit, Hussein Al‐Mossawi, Michael H. Hühn, Carolina V. Arancibia-Cárcamo et autres

gb, us (code pays fourni par la source)

RORgT modulates key features in adult thymopoiesis (HEM2P.235)

Yanxia Guo, Kenzie D. MacIsaac, Abbas Hawwari, Richard B. Miller et autres

Abstract Recent studies have elucidated the molecular mechanism of RORgT transcriptional network controlling Th17 cell lineage fate and effector function. RORgT was initially identified as a transcription factor required for thymopoiesis by maintaining survival of CD4+CD8+ (DP) thymocytes. There are increasing efforts …

us (code pays fourni par la source)

Anti-inflammatory actions of Chemoattractant Receptor-homologous molecule expressed on Th2 by the antagonist MK-7246 in a novel rat model of Alternaria alternata elicited pulmonary inflammation

Malgorzata A. Gil, Michael Caniga, Janice D. Woodhouse, Joseph B. Eckman et autres

Alternaria alternata is a fungal allergen linked to the development of severe asthma in humans. In view of the clinical relationship between A. alternata and asthma, we sought to investigate the allergic activity of this antigen after direct application to the lungs …

us (code pays fourni par la source)

Biased Ligand Modulation of Seven Transmembrane Receptors (7TMRs): Functional Implications for Drug Discovery

Craig C. Correll, Brian A. McKittrick

Seven transmembrane receptors (7TMRs), also known as G-protein-coupled receptors (GPCRs), have proven to be valuable targets for the development of therapeutics. The expansion of our understanding of 7TMR downstream signaling pathways beyond G-proteins has broadened our appreciation of the versatility of these …

us (code pays fourni par la source)

Quality by design (QbD) of amide isosteres: 5,5-Disubstituted isoxazolines as potent CRTh2 antagonists with favorable pharmacokinetic and drug-like properties

Dong Xiao, Xiaohong Zhu, Younong Yu, Ning Shao et autres

us (code pays fourni par la source)

Pharmacological characterization of the late phase reduction in lung functions and correlations with microvascular leakage and lung edema in allergen-challenged Brown Norway rats

Peter J. Mauser, Aileen House, Howard Jones, Craig C. Correll et autres

us (code pays fourni par la source)

Pharmacological Characterization Of The Late Phase Reduction In Forced Vital Capacity (FVC) In Allergen-Challenged Brown Norway Rats: Correlations With Lung Edema

Peter J. Mauser, Richard W. Chapman, Howard Jones, Aileen House et autres