|
|
| Type |
Poster Presentation |
| Area |
Life Chemistry |
| Room No. |
Exhibition Hall 2 |
| Time |
4월 19일 (금요일) 11:00~12:30 |
| Code |
LIFE.P-349 |
| Subject |
Identification and Characterization of Novel Leads from a Kinase-Focused Compound Library for Hepatocyte Growth Factor Receptor (HGFR) |
| Authors |
Hyun Ho Jeong, Jinho Lee*, Victor Sukbong Hong*
Department of Chemistry, Keimyung University, Korea
|
| Abstract |
Hepatocyte growth factor receptor (HGFR), also called c-MET, is a transmembrane tyrosine kinase which is encoded by the MET gene. HGFR is associated with cell proliferation, motility, migration and invasion. Although HGFR plays an important role in regulating tissue homeostasis, it is also known that overexpressed HGFR has been implicated in cancer angiogenesis and metastasis. Hence, development of small molecular inhibitors to block the activity of HGFR can be a good way to treat the cancer. We have used a time-resolved fluorescence resonance energy transfer (TR-FRET) assay to identify small molecule inhibitors of HGFR. By screening a kinase-focused library of 333 compounds at 10 M concentration, we identified a group of compounds with a 3,4,5-trisubstituted indoline as a common core structure that inhibits HGFR activity. To understand the mechanism of inhibition of 3,4,5-trisubstituted indoline against HGFR, we carried out mechanistic studies with KMU010642 which is the most potent compound from screening. Kinetic analysis demonstrates that KMU010642 is competitive with ATP. |
| E-mail |
ii7773@naver.com |
|
123rd General Meeting of the KCS