期刊
ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
卷 21, 期 3, 页码 89-96出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/adt.2022.116
关键词
serotonin; 5-HT2B; pulmonary arterial hypertension; high-throughput screen
A high-throughput screen campaign led to the discovery of highly potent and selective 5-HT2B antagonists. Selected compounds were also evaluated for their ability to cross the blood-brain barrier. Two compounds, VU0530244 and VU0631019, showed limited potential for brain penetration, making them promising candidates for the development of 5-HT2B antagonists without centrally-mediated adverse effects.
Antagonists of the serotonin receptor 2B (5-HT2B) have shown great promise as therapeutics for the treatment of pulmonary arterial hypertension, valvular heart disease, and related cardiopathies. Herein, we describe a high-throughput screen campaign that led to the identification of highly potent and selective 5-HT2B antagonists. Furthermore, selected compounds were profiled for their predicted ability to cross the blood-brain barrier. Two exemplary compounds, VU0530244 and VU0631019, were predicted to have very limited potential for brain penetration in human subjects, a critical profile for the development of 5-HT2B antagonists devoid of centrally-mediated adverse effects.
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