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Updated: Jun 15, 2025

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
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From lab to clinic: The discovery and optimization journey of PI3K inhibitors

Siyu Lian1, Zhenhua Du1, Qingqing Chen1

  • 1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

European Journal of Medicinal Chemistry
|August 24, 2024
PubMed

Insights

This review traces the development of phosphoinositide 3-kinase (PI3K) inhibitors, from initial lab discovery to clinical use. It highlights optimization strategies and clinical trial progress for these promising cancer therapeutics.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • The phosphoinositide 3-kinase (PI3K) pathway is crucial in cellular functions and frequently dysregulated in cancers.
  • PI3K inhibitors represent a significant therapeutic strategy for various malignancies.
  • Understanding the PI3K pathway's role is key to developing targeted cancer therapies.

Purpose of the Study:

  • To review the historical development and evolutionary path of PI3K inhibitors.
  • To examine the transition of PI3K inhibitors from laboratory research to clinical applications.
  • To assess the optimization strategies, clinical trials, challenges, and future prospects of PI3K inhibitors.

Main Methods:

  • Literature review of PI3K signaling and inhibitor development.
  • Analysis of medicinal chemistry and structural modification approaches for PI3K inhibitors.
  • Examination of preclinical data and clinical trial outcomes for PI3K inhibitors.

Main Results:

  • Fundamental discoveries in PI3K signaling paved the way for inhibitor development.
  • Medicinal chemistry efforts improved PI3K inhibitor potency, selectivity, and pharmacokinetics.
  • Clinical trials have evaluated the efficacy and safety of PI3K inhibitors, facing specific challenges.

Conclusions:

  • PI3K inhibitors have evolved significantly from discovery to clinical application.
  • Continued research and development are crucial for optimizing PI3K inhibitors' therapeutic potential.
  • These agents hold promise for improved cancer treatment outcomes.
Keywords:
Cancer therapyClinical trialsContentDrug developmentPI3K pathwayTargeted therapy

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