A Drug with Lipophilicity-Dependent Potency Can Be Metabolically Stable: Discovery of a Potent and Selective Retinoic Acid Receptor-Related Orphan Receptor C2 (RORC2) Inverse Agonist as an Orally Bioavailable Anti-Inflammatory Agent

doi:10.1021/acs.jmedchem.8b01545

	A Drug with Lipophilicity-Dependent Potency Can Be Metabolically Stable: Discovery of a Potent and Selective Retinoic Acid Receptor-Related Orphan Receptor C2 (RORC2) Inverse Agonist as an Orally Bioavailable Anti-Inflammatory Agent
	Wang, Yibing; Liu, Hong
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2018-12-13
卷号	61 期号:23 页码:10412-10414
ISSN号	0022-2623
DOI	10.1021/acs.jmedchem.8b01545
文献子类	Article
英文摘要	IL-17 drives an amplification mechanism in inflammatory diseases such as psoriasis, psoriatic arthritis, and ankylosing spondylitis. The production of IL-17 depends on the activity of RORC2 in immune cells, which suggests that RORC2 inverse agonists are capable of anti-inflammatory therapy by reducing IL-17 levels. However, oral delivery of inverse agonists remains a challenge since the binding pocket of RORC2 prefers to accommodate lipophilic ligands, which tend to have poor metabolic stability. This Viewpoint discusses recent results published in this journal that identified a potent, selective, and orally bioavailable RORC2 inverse agonist as an anti-inflammatory agent, optimized from a high-throughput screening (HTS) hit through a combination of de novo and structure-guided design.
WOS关键词	GAMMA
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000453488200005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279469]
专题	药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Liu, Hong
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Yibing,Liu, Hong. A Drug with Lipophilicity-Dependent Potency Can Be Metabolically Stable: Discovery of a Potent and Selective Retinoic Acid Receptor-Related Orphan Receptor C2 (RORC2) Inverse Agonist as an Orally Bioavailable Anti-Inflammatory Agent[J]. JOURNAL OF MEDICINAL CHEMISTRY,2018,61(23):10412-10414.
APA	Wang, Yibing,&Liu, Hong.(2018).A Drug with Lipophilicity-Dependent Potency Can Be Metabolically Stable: Discovery of a Potent and Selective Retinoic Acid Receptor-Related Orphan Receptor C2 (RORC2) Inverse Agonist as an Orally Bioavailable Anti-Inflammatory Agent.JOURNAL OF MEDICINAL CHEMISTRY,61(23),10412-10414.
MLA	Wang, Yibing,et al."A Drug with Lipophilicity-Dependent Potency Can Be Metabolically Stable: Discovery of a Potent and Selective Retinoic Acid Receptor-Related Orphan Receptor C2 (RORC2) Inverse Agonist as an Orally Bioavailable Anti-Inflammatory Agent".JOURNAL OF MEDICINAL CHEMISTRY 61.23(2018):10412-10414.