title: Identification of two novel α1-AR agonists using a high-throughput screening model.
abstract: α1-Adrenoceptors (ARs; 1A, 1B, and 1D) have been determined to perform different prominent functions in the physiological responses of the sympathetic nervous system. A high-throughput screening assay (HTS) was set up to detect α1-AR subtype-selective agonists by a dual-luciferase reporter assay in HEK293 cells. Using the HTS assay, two novel compounds, CHE3 and CHK3, were discovered as α1-ARs agonists in α1-ARs expressed in HEK293 cells. These compounds also showed moderate/weak anti-proliferative activities against tested cancer cell lines. The HTS assay proposed in this study represents a potential method for discovering more α1-AR subtype-selective ligands.
authors.affiliation: Pharmaceutical Research Center, Guangzhou Medical University, 195# Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.affiliation: Pharmaceutical Research Center, Guangzhou Medical University, 195# Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Pharmaceutical Research Center, Guangzhou Medical University, 195# Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Xuelan
authors.initials: X
authors.lastname: He
authors.affiliation: Pharmaceutical Research Center, Guangzhou Medical University, 195# Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Xu
authors.affiliation: Pharmaceutical Research Center, Guangzhou Medical University, 195# Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Xu
authors.affiliation: Pharmaceutical Research Center, Guangzhou Medical University, 195# Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Biyun
authors.initials: B
authors.lastname: Huang
authors.affiliation: Pharmaceutical Research Center, Guangzhou Medical University, 195# Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Liang
authors.affiliation: Pharmaceutical Research Center, Guangzhou Medical University, 195# Dongfengxi Road, Guangzhou 510182, China. mryuanmu838@sina.com.
authors.forename: Mu
authors.initials: M
authors.lastname: Yuan
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000737:chemistry / Q000302:isolation & purification*; D049109:Cell Proliferation / Q000187:drug effects; D057809:HEK293 Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D008024:Ligands; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D013564:Sympathetic Nervous System / Q000187:drug effects*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D008024:Ligands; D018340:Receptors, Adrenergic, alpha-1