Identification of Potent, Selective, and Peripherally Restricted Serotonin Receptor 2B Antagonists from a High-Throughput Screen
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Assay and drug development technologies - 21(2023), 3 vom: 01. Apr., Seite 89-96 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bender, Aaron M [VerfasserIn] |
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| Links: |
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| Themen: |
333DO1RDJY |
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| Anmerkungen: |
Date Completed 12.04.2023 Date Revised 02.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1089/adt.2022.116 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354362542 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
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| 700 | 1 | |a Days, Emily |e verfasserin |4 aut | |
| 700 | 1 | |a Lindsley, Craig W |e verfasserin |4 aut | |
| 700 | 1 | |a Merryman, W David |e verfasserin |4 aut | |
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