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| Type |
Poster Presentation |
| Area |
Medicinal Chemistry |
| Room No. |
Exhibition Hall 2 |
| Time |
4월 18일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-378 |
| Subject |
Design, Synthesis and biological evaluation of novel pyrimidine derivatives as NUAK1 kinase inhibitors
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| Authors |
JaeHo Kim, Sora Paik1, So Ha Lee2,*, Jongseung Kim*
Department of Chemistry, Korea University, Korea
1Korea Institute of Science and Technology, Korea
2Chemical Kinomics Research Center, Korea Institute of Science and Technology, Korea
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| Abstract |
Abstract
Cancer cells grow by the signal transduction pathway like normal cells and there are various protein kinases in the cell that play an important role in the signaling pathway. Until recently, it has been known that among the various kinases, NUAK kinase has two types of NUAK1, NUAK2. NUAK kinase is a serine / threonine protein kinase belonging to the AMP-activating protein kinase (AMPK) family and (AMPK) is a critical regulator of cellular and whole-body energy homeostasis with potential therapeutic targets. ARK5, AMPK – related protein kinase meditating Akt signals, is closely involved in tumor progression, and its stage-associated expression was observed in colorectal cancer. Also, (NUAK) has been reported to promote tumor progression and metastatic capacity via the upregulation of cell proliferation, inhibition of p53-mediated tumor suppression, and increased matrix metalloproteinases (MMPs) in various cancer. More recently, a key finding showing that NUAK1 (also known as ARK5) may play a role in regulating tumor proliferation and survival through metabolic alteration in hepatocarcinoma demonstrated that targeting cellular energy homeostasis could be a valuable strategy to eliminate Myc-deregulated tumor cells. Therefore, inhibition of NUAK1 can be an effective therapeutic strategy in these diseases. For developing NUAK1 inhibitors, From high-throughput screening, we found hit compounds, and synthesized new pyrimidine derivatives based on the hit scaffolds. Among the synthesized compounds, KIST301670 was identified as a potent NUAK1 inhibitor. The optimization of novel NUAK1 inhibitors to further enhance potency and physicochemical properties is now in progress.
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| E-mail |
woghtlsghk@naver.com |
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123rd General Meeting of the KCS