Development of small-molecule inhibitors that target PI3Kβ

Phosphatidylinositol-3 kinase (PI3K) β, a subtype of class I PI3Ks, has an essential role in PTEN-deficient tumors and links to thrombosis, male fertility, and Fragile X syndrome. PI3Kβ-specific targeting therapy could be an efficacious treatment for diseases highly dependent on PI3Kβ, while mitigat...

Full description

Saved in:
Bibliographic Details
Published inDrug discovery today p. 103854
Main Authors Yu, Yanzhen, Gu, Dongyan, Cai, Lvtao, Yang, Haodong, Sheng, Rong
Format Journal Article
LanguageEnglish
Published England 07.12.2023
Subjects
thrombosis
selective inhibition
PI3Kβ
PTEN-null cancers
atropisomerism
Online AccessGet full text

Cover

More Information
Summary:Phosphatidylinositol-3 kinase (PI3K) β, a subtype of class I PI3Ks, has an essential role in PTEN-deficient tumors and links to thrombosis, male fertility, and Fragile X syndrome. PI3Kβ-specific targeting therapy could be an efficacious treatment for diseases highly dependent on PI3Kβ, while mitigating the severe toxicity of pan-PI3K inhibitors. Achieving selectivity can be accomplished through three primary strategies, namely, binding to the induced lipophilic pocket, targeting the unique amino acid residue of PI3Kβ, or using atropisomerism to lock conformation. In this review, we focus on advances in the development of these β-isoform-selective PI3K inhibitors, providing potential guidance for the further development of novel clinical candidates.
ISSN:1878-5832