Sonolisib: Pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, Oncolytic

Arun Azad, Kim N Chi

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The phosphatidylinositol 3-kinase (PI3K) enzymes are key signal transduction molecules that control cellular processes frequently dysregulated in cancer, including cell growth, metabolism, proliferation, survival and angiogenesis. The PI3K family comprises three classes (I-III), of which class IA PI3K is most strongly associated with malignancy and accordingly represents an important therapeutic target. Early-generation PI3K inhibitors, such as wortmannin and LY-294002, were plagued by numerous problems, including poor target specificity, suboptimal pharmacokinetics and unacceptable toxicity. More recently, novel PI3K inhibitors with superior pharmacological properties have emerged. One of these is sonolisib (PX-866), a derivative of wortmannin and an irreversible and potent pan-isoform inhibitor of class IA PI3K. Sonolisib has shown encouraging preclinical activity and is currently undergoing clinical development in prostate cancer, glioblastoma, melanoma, head and neck squamous cell cancer, non-small cell lung cancer and colorectal cancer. This review summarizes the pharmacology, preclinical data and clinical studies of sonolisib in cancer.
Original languageEnglish
Pages (from-to)299 - 308
Number of pages10
JournalDrugs of the Future
Volume38
Issue number5
DOIs
Publication statusPublished - 2013
Externally publishedYes

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