These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Structure-based identification of novel CK2 inhibitors with a linear 2-propenone scaffold as anti-cancer agents.
    Author: Qi X, Zhang N, Zhao L, Hu L, Cortopassi WA, Jacobson MP, Li X, Zhong R.
    Journal: Biochem Biophys Res Commun; 2019 Apr 30; 512(2):208-212. PubMed ID: 30878184.
    Abstract:
    Protein kinase CK2 has emerged as an attractive cancer therapeutic target. Previous studies have highlighted the challenge of optimizing CK2 ATP-competitive inhibitors that have low druggability due to their polycyclic ring scaffolds. Therefore the development of novel inhibitors with non-polycyclic scaffolds emerges as a promising strategy for drug discovery targeting CK2. In this current study, based on the similar predicted binding poses of the linear 2-propenone scaffold of isoliquiritigenin with that of the polycyclic inhibitor CX-4945, a series of 2-propenone derivatives containing an amine-substituted five-membered heterocycle and a benzoic acid were designed, synthesized and evaluated for their in vitro CK2 inhibition and anti-cancer activity. Compound 8b was found to be the most potent CK2 inhibitor (IC50 = 0.6 μM) with the anti-proliferative activity on HepG2 cancer cells (IC50 = 14 μM), compared to the activity of isoliquiritigenin (IC50 = 17 μM and 51 μM, respectively). Molecular docking was performed to understand the binding modes of the newly designed 2-propenone derivatives with CK2. Compound 8b formed the most favorable network of hydrogen bonds with both the hinge region and positive area. Our results indicate that CK2 derivatives with a linear 2-propenone scaffold are promising candidates for anti-cancer drug discovery.
    [Abstract] [Full Text] [Related] [New Search]