Structure, function and inhibition of the phosphoinositide 3-kinase p110α enzyme

The PI3K (phosphoinositide 3-kinase) p110 alpha isoform is activated by oncogenic mutations in many cancers. This has stimulated intense interest in identifying inhibitors of the PI3K pathway as well as p110 alpha-selective inhibitors, and understanding the mechanisms underlying activation by the oncogenic mutations. In the present article, we review recent progress in the structure and function of the p110 alpha enzyme and two of its most common oncogenic mutations, the development of isoform-selective inhibitors, and p110 alpha pharmacology.