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Updated: Jul 20, 2025

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach
11:11

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Published on: February 21, 2019

7.5K

Synthesis and Anticancer Activity of Novel Dual Inhibitors of Human Protein Kinases CK2 and PIM-1

Patrycja Wińska1, Monika Wielechowska1, Mirosława Koronkiewicz2

  • 1Faculty of Chemistry, Warsaw University of Technology, 00-664 Warsaw, Poland.

Pharmaceutics
|July 29, 2023
PubMed

Insights

Novel dual inhibitors targeting CK2 and PIM-1 kinases were synthesized. The lead compound, a trifluoro-propanol derivative, effectively reduced cancer cell viability, induced apoptosis, and promoted autophagy, particularly in acute lymphoblastic leukemia cells.

Area of Science:

  • Medicinal Chemistry
  • Cancer Biology
  • Molecular Pharmacology

Background:

  • Serine/threonine kinases CK2 and PIM-1 regulate critical cellular processes like proliferation and apoptosis.
  • Inhibiting CK2 and PIM-1 kinase activity can decrease cancer cell viability by inducing apoptosis.

Purpose of the Study:

  • To design and synthesize novel dual CK2/PIM-1 inhibitors based on the DMAT scaffold.
  • To evaluate the anti-cancer potential of these novel compounds against human carcinoma cell lines.

Main Methods:

  • Synthesis of novel amino alcohol derivatives of DMAT.
  • In vitro kinase inhibition assays for CK2 and PIM-1.
  • MTT assay to assess cancer cell viability.
  • Flow cytometry for apoptosis and cell cycle analysis.
  • Western blot and fluorescence assays for autophagy and intracellular kinase inhibition.

Main Results:

  • A novel trifluoro-propanol derivative showed high selectivity and potent pro-apoptotic effects on cancer cells, especially acute lymphoblastic leukemia.
  • The lead compound induced apoptosis and autophagy in K-562 leukemia cells.
  • Intracellular inhibition of CK2 and PIM-1 was confirmed in tested cancer cell lines.

Conclusions:

  • Novel dual CK2/PIM-1 inhibitors demonstrate significant anti-cancer activity.
  • The lead compound exhibits promising therapeutic potential for treating specific cancers, including acute lymphoblastic leukemia.
  • Further investigation into the mechanism of action, including autophagy induction, is warranted.
Keywords:
4,5,6,7-tetrabromo-N,N-dimethyl-1H-benzimidazol-2-amine (DMAT) derivativesantitumor activityapoptosisautophagydual protein kinase inhibitorsprotein kinase CK2protein kinase PIM-1

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