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Published on: February 21, 2019

Targeted small-molecule inhibitors of protein kinase B as anticancer agents

Ian Collins1

  • 1Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Surrey SM2 5NG, UK. ian.collins@icr.ac.uk

Anti-Cancer Agents in Medicinal Chemistry
|January 20, 2009
PubMed

Insights

Small molecule inhibitors targeting Protein Kinase B (PKB or Akt) are crucial for cancer therapy. Structure-based design has advanced the development of potent and selective PKB inhibitors, with some now in clinical trials.

Area of Science:

  • Oncology
  • Pharmacology
  • Structural Biology

Background:

  • Protein Kinase B (PKB or Akt) is a key regulator in the PI3K-PKB-mTOR signaling pathway.
  • Dysregulation of PKB signaling is implicated in various cancers, making it a significant therapeutic target.

Purpose of the Study:

  • To review the development of small molecule inhibitors targeting PKB for anticancer therapy.
  • To highlight the role of structural biology in designing potent and selective PKB inhibitors.

Main Methods:

  • Review of small molecule PKB inhibitors with diverse mechanisms of action (e.g., ATP-competitive, allosteric).
  • Emphasis on structure-based drug design strategies for lead generation and optimization.
  • Analysis of approaches to enhance compound pharmacodynamics, efficacy, and therapeutic window.

Main Results:

  • Several classes of PKB inhibitors have been developed, utilizing various inhibition mechanisms.
  • Structure-based design has been instrumental in optimizing inhibitor potency and selectivity.
  • Early-stage clinical trials are underway for selective PKB inhibitors, with promising preclinical data for others.

Conclusions:

  • Small molecule inhibitors targeting PKB represent a promising avenue for anticancer drug development.
  • Continued application of structure-based design is vital for advancing PKB-targeted therapies.
  • The field is progressing rapidly, with several inhibitors showing potential for clinical success.

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