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Updated: Sep 22, 2025

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

Published on: February 21, 2019

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Identification of novel natural inhibitors targeting AKT Serine/Threonine Kinase 1 (AKT1) by computational study

Sheng Zhong1, Zhiyun Zhang2, Zhen Guo2

  • 1Neurosurgery and Neuro-Oncology Department, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Bioengineered
|May 23, 2022
PubMed

Insights

Researchers identified novel AKT1 inhibitors to improve cancer treatment. These compounds show potential for inhibiting tumor cell growth and AKT1 expression, offering new therapeutic avenues with reduced toxicity.

Area of Science:

  • Oncology
  • Medicinal Chemistry
  • Biochemistry

Background:

  • Current cancer therapies face challenges with toxicity and limited efficacy.
  • The PI3K/AKT/mTOR pathway is crucial in tumor development, making AKT1 a key therapeutic target.
  • Existing AKT1 inhibitors like Ipatasertib are used, but there is a need for improved drug candidates.

Purpose of the Study:

  • To discover and characterize novel, potent AKT1 inhibitors.
  • To lay the groundwork for developing improved AKT1-targeted cancer therapies.
  • To identify drug candidates with enhanced properties and reduced toxicity.

Main Methods:

  • Utilized the ZINC15 database and Discovery Studio 4.5 for computer-aided drug screening (virtual screening, ADME, TOPKAT, MD simulations).
  • Employed structural and biochemical methods to evaluate inhibitor candidates.
  • Conducted cell-based assays (CCK8, ELISA) to assess efficacy and inhibition of AKT1 expression in MG63 osteosarcoma cells.

Main Results:

  • Identified novel compounds with potential for AKT1 inhibition.
  • MD simulations confirmed stable binding of inhibitors with AKT1.
  • Cell experiments demonstrated inhibition of MG63 cell proliferation and AKT1 expression by the novel compounds.
  • Compounds exhibited favorable ADME properties and higher tolerance to cytochrome P4502D6.

Conclusions:

  • Novel AKT1 inhibitors were successfully identified through computational and experimental approaches.
  • These compounds show promise for developing next-generation AKT1-targeted cancer drugs.
  • Structural modifications offer a basis for rational drug design targeting AKT1 in cancer treatment.
Keywords:
AKT1CCK8ELISAdiscovery studiodrug treatmentipatasertibvirtual screening

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