A comprehensive review of small molecules targeting PI3K pathway: Exploring the structural development for the...

Area of Science:

• Oncology
• Medicinal Chemistry
• Pharmacology

Background:

• Breast cancer is a leading cause of cancer-related mortality globally, particularly in females.
• Aberrant activation of the Phosphatidylinositol 3-Kinase (PI3K) pathway is a key driver of breast cancer cell survival and proliferation.
• Targeting the PI3K pathway is a critical therapeutic strategy in breast cancer treatment.

Purpose of the Study:

• To review current advancements in anti-cancer drug development targeting PI3K over-activation in breast cancer.
• To explore structural activity relationships (SAR) of PI3K inhibitors for breast cancer therapy.
• To provide an overview of PI3K inhibitors in clinical trials and their therapeutic implications.

Main Methods:

• Literature review of scientific articles and clinical trial data on PI3K inhibitors for breast cancer.
• Analysis of structural activity relationships (SAR) for various heterocyclic small molecules targeting PI3K.
• Examination of approved and investigational PI3K inhibitors, including their efficacy and side effect profiles.

Main Results:

• Several heterocyclic moieties, including triazines, pyrimidines, quinazolines, quinolines, and pyridoxines, show potential as PI3K inhibitors.
• Orally available PI3K inhibitors like Alpelisib (FDA-approved) are in clinical use, alongside others such as buparlisib, pictilisib, and taselisib.
• Current PI3K inhibitors demonstrate therapeutic benefits but are associated with significant side effects and high costs.

Conclusions:

• Targeting the PI3K pathway remains a promising strategy for breast cancer treatment.
• Continued research into SAR is crucial for developing more effective and safer PI3K inhibitors.
• Addressing side effects and cost remains a challenge for current PI3K-targeted breast cancer therapies.