|
|
| Type |
Poster Presentation |
| Area |
Medicinal Chemistry |
| Room No. |
Event Hall |
| Time |
4월 19일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-597 |
| Subject |
Screening for discovery of a potent and selective Inhibitor for CBP Bromodomain |
| Authors |
Nalee Kim, Hak Joong Kim*
Department of Chemistry, Korea University, Korea
|
| Abstract |
Post-transcriptional modifications of chromatin are key mechanisms in regulation of DNA transcription, often called “epigenetic regulation”. Bromodomains are key epigenetic regulators whose functions are to recognize acetyllysine marks (Kac) on various proteins including histones. Discovery of selective inhibitors targeting bromodomains can improve our understanding of the physiological functions of bromodomains and, in addition, it can provide a new therapeutic strategy to treat various diseases such as cancer. Among >50 bromodomains found in human, our study has been focused on discovery of a potent and selective inhibitor for the CREB binding protein bromodomain (abbreviated as CBP bromdomain), one of the non-BET type bromodomains.
This study was initiated with an activity screening of small molecule library (>6000 compounds). Specifically, the bromodomain region among the CBP was cloned to construct an expression plasmid for purification of CBP bromodomain protein. Then, a screening campaign was conducted based on the thermal shift assay to monitor the change of the melting temperature of CBP bromodomain, of which elevation corresponds to the binding of a potent inhibitor. With a number of hit compounds identified, a docking study was performed to predict their binding modes within the active site of CBP bromodomain, which would provide an important foundation for rational optimization of the inhibitor structure as well as potency.
|
| E-mail |
dowhg1@korea.ac.kr |
|
121st General Meeting of the KCS