Year: 2020
Type: article
Abstract: REV-ERBα (NR1D1) is a circadian clock component that functions as a transcriptional repressor.Due to its role in direct modulation of metabolic genes, REV-ERBα is regarded as an integrator of cell metabolism with circadian clock.Accordingly, REV-ERBα is first proposed as a drug target for treating sleep disorders and metabolic syndromes (e.g., dyslipidaemia, hyperglycaemia and obesity).Recent years of studies uncover a rather broad role of REV-ERBα in pathological conditions including local inflammatory diseases, heart failure and cancers.Moreover, REV-ERBα is involved in regulation of circadian drug metabolism that has implications in chronopharmacology.In the meantime, recent years have witnessed discovery of an array of new REV-ERBα ligands most of which have pharmacological activities in vivo.In this article, we review the regulatory role of REV-ERBα in various types of diseases and discuss the underlying mechanisms.We also describe the newly discovered ligands and the old ones together with their targeting potential.Despite well-established pharmacological effects of REV-ERBα ligands in animals (preclinical studies), no progress has been made regarding their translation to clinical trials.This implies certain challenges associated with drug development of REV-ERBα ligands.In particular, we discuss the potential challenges related to drug safety (or adverse effects) and bioavailability.For new drug development, it is advocated that REV-ERBα should be targeted to treat local diseases and a targeting drug should be locally distributed, avoiding the adverse effects on other tissues.
Source: Theranostics
DOI: 10.7150/thno.43834
Authors: Shuai Wang, Feng Li, Yanke Lin, Baojian Wu
Institution: Jinan University
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,671
Awards: G4853963241, G6653352185
OpenAlex ID: W3012674235