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Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
Virtual Screening and Biological Activity Evaluation of New Potent Inhibitors Targeting Hexokinase-II
1College of Physical Education, Northwest Normal University, Lanzhou 730070, China.
Abstract:
Hexokinase-II (HK-II), the rate-limiting step enzyme in the glycolysis pathway, expresses high levels of cancer cells compared with normal cells. Due to its pivotal role in the different aspects of cancer physiology including cellular proliferation, metastasis, and apoptosis, HK-II provides a new therapeutic target for cancer therapy. The structure-based virtual screening targeting HK-II was used to hit identifications from small molecule databases, and the select compounds were further evaluated in biological assays. Forty-seven compounds with the lowest binding energies were identified as potential HK-II inhibitors. Among them, nine compounds displayed the highest cytotoxicity to three different cancer cells. Based on the mechanism study, compounds 4244-3659 and K611-0094 showed an obvious inhibitory effect on the HK-II enzyme. This study identified two potential inhibitors of HK-II and can be helpful for developing potential drugs targeting HK-II in tumor therapy.
Insights
Researchers identified two novel compounds that inhibit Hexokinase-II (HK-II), a key enzyme in cancer cell metabolism. These findings offer potential new therapeutic strategies for cancer treatment by targeting HK-II.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Hexokinase-II (HK-II) is crucial for glycolysis and highly expressed in cancer cells.
- HK-II plays a vital role in cancer cell proliferation, metastasis, and apoptosis, making it a therapeutic target.
Purpose of the Study:
- To identify novel small molecule inhibitors of Hexokinase-II (HK-II) through structure-based virtual screening.
- To evaluate the inhibitory potential and cytotoxicity of identified compounds against cancer cells.
Main Methods:
- Structure-based virtual screening of small molecule databases to identify potential HK-II inhibitors.
- Biological assays were conducted to evaluate the cytotoxicity and enzyme inhibitory effects of selected compounds.
Main Results:
- Forty-seven compounds with low binding energies were identified as potential HK-II inhibitors.
- Nine compounds exhibited significant cytotoxicity against three different cancer cell lines.
- Compounds 4244-3659 and K611-0094 demonstrated clear inhibitory effects on HK-II enzyme activity.
Conclusions:
- Two compounds, 4244-3659 and K611-0094, were identified as potent HK-II inhibitors.
- These compounds show promise for the development of novel anti-cancer drugs targeting HK-II in tumor therapy.
