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A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

AKT crystal structure and AKT-specific inhibitors

Chandra C Kumar1, Vincent Madison

  • 1Department of Tumor Biology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. chandra.kumar@spcorp.com

Oncogene
|November 17, 2005
PubMed

Insights

Targeting AKT kinases, crucial for cancer cell survival, is a promising strategy for new drug discovery. This review details AKT inhibitors, structural insights, and challenges in developing effective cancer therapeutics.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • AKT kinases play a critical role in tumor cell survival and proliferation.
  • Overexpression and activation of AKT kinases are observed in numerous human cancers, making them attractive therapeutic targets.

Purpose of the Study:

  • To review the rationale and recent progress in targeting AKT kinases for drug discovery.
  • To summarize structural features, inhibitor development, and challenges in creating AKT-targeted therapeutics.

Main Methods:

  • Analysis of crystal structures of AKT kinase in inactive and active states.
  • Review of small molecule inhibitors targeting the ATP binding site, PH domain, and protein substrate binding site.
  • Discussion of structure-based design, computer modeling, and allosteric inhibitor development.

Main Results:

  • Various small molecule inhibitors targeting different sites of AKT kinase have been developed.
  • Structural studies provide insights into AKT kinase's inactive and active conformations, aiding inhibitor design.
  • Development of isoform-selective allosteric inhibitors shows promise.

Conclusions:

  • Targeting AKT kinases remains a key strategy in cancer drug discovery.
  • Challenges in developing selective and effective AKT inhibitors persist, requiring further research.
  • Continued exploration of diverse inhibitor classes and design strategies is essential for therapeutic advancement.

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