A rticle Inhibitors of Phosphatidylinositol 3-kinases: The Next Wave of Anti-Cancer Drugs?

Phosphatidylinositol 3-kinases (PI3Ks) are a family of lipid kinase enzymes, which catalyse the phosphorylation of the 3′-hydroxyl position of the inositol ring of phospha-tidylinositol 4,5-diphosphate (PIP 2) to give the messenger molecule phosphatidylinositol 3,4,5-triphosphate (PIP 3 (Scheme 1). This then participates in a variety of physi-ological processes, including cell growth and differentia-tion.1 The PI3Ks are divided into three classes (I-III) based on their structure, mode of regulation, and substrate speci-ficity. Class 1A PI3Ks are comprised of three isoforms (p110α, p110β and p110δ) that share a common regula-tory subunit (p85) activated by signals from receptor pro-tein tyrosine kinases, while the Class IB PI3K (p110γ) i