Abstract |
Recent advances in basic and clinical studies have identified Rho kinase (ROCK) as an important target potentially implicated in a variety of cardiovascular diseases and ROCK inhibitors were considered as a pharmacological strategy to prevent and treat cardiovascular diseases. To screen the small molecule compound library against ROCK, a high throughput screening (HTS) campaign was carried out using immobilized metal affinity for phosphochemicals ( IMAP)-based time-resolved fluorescence resonance energy transfer (TR-FRET) assay. Z' value and signal to background (S/B) ratio were achieved at 0.76 and 5.27 for the pilot library screening of the most diverse set consisting of 15,040 compounds with a reasonable reconfirmation rate. From this screening campaign, four novel scaffolds, such as 3- nitropyridine, 4-methoxy-1,3,5,-triazine, naphthalene-1,4-dione, and 2,3-dihydro-1H-pyrrolo[2,3-b] quinoxaline, were yielded. Particularly, we found that 3-nitropyridine derivatives possess potent inhibitory activity and selectivity for ROCK. Our findings provide important information for the design of novel ROCK inhibitor.
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Authors | Kwang-Seok Oh, Jihye Mun, Jae Eun Cho, Sunghou Lee, Kyu Yang Yi, Chae Jo Lim, Jin Soo Lee, Whui Jung Park, Byung Ho Lee |
Journal | Combinatorial chemistry & high throughput screening
(Comb Chem High Throughput Screen)
Vol. 16
Issue 1
Pg. 37-46
(Jan 2013)
ISSN: 1875-5402 [Electronic] United Arab Emirates |
PMID | 22934984
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Protein Kinase Inhibitors
- Small Molecule Libraries
- ROCK2 protein, human
- rho-Associated Kinases
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Topics |
- Drug Design
- Drug Evaluation, Preclinical
(methods)
- High-Throughput Screening Assays
(methods)
- Humans
- Models, Molecular
- Protein Kinase Inhibitors
(chemistry, pharmacology)
- Small Molecule Libraries
(chemistry, pharmacology)
- rho-Associated Kinases
(antagonists & inhibitors, metabolism)
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