Hybridization-based discovery of novel quinazoline-2-indolinone derivatives as potent and selective PI3Kα inhibitors.

ABSTRACT:

Introduction

Phosphatidylinositol 3-kinases (PI3Ks) overexpression can elicit cellular homeostatic dysregulation, which further contributes to tumorigenesis, with PI3Kα emerging as the most prevalent mutant isoform kinase among PI3Ks. Therefore, selective inhibitors targeting PI3Kα have attracted considerable interest in recent years. Molecular hybridization, with the advantage of simplified pharmacokinetics and drug-drug interactions, emerged as one of the important avenues for discovering potential drugs.

Objectives

This study aimed to construct PI3Kα inhibitors by hybridization and investigate their antitumor activity and mechanism.

Methods

26 quinazoline-2-indolinone derivatives were obtained by molecular hybridization, and their structure-activity relationship wa

SUBMITTER: Liu C 

PROVIDER: S-EPMC11785560 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature