“PI3K” is sometimes used in the singular, but in fact, the PI3 kinases are a group of eight enzymes that can be sorted into three classes. In general, a PI3K is made up of a catalytic subunit, which does the phosphorylation, and a regulatory subunit. The catalytic subunit, or p110, of class 1 PI3Ks can be of four different types, or isoforms, α,β,γ, and δ. In the work recently reported in Nature, the scientists targeted the δ isoform of the p110 catalytic subunit.
Different drugs target different isoforms. In addition, there are other kinases that have structural similarities to PI3K, and they, too, can be shut down by the right “PI3K” inhibitor.
What at first blush seems like a recipe for off-target effects can, with a thorough understanding of the relationship between different isoforms and the inhibitors that target them, be used to match the pattern of inhibition to what is needed for a specific task.
ChemDiv’s PI3K targeted Libraries:• TK Targeted Library
• PI3K-Targeted Library
For example, PI3K was shown to play a role several years ago in metabolic signaling. It is intimately connected with another kinase, mTOR, which senses the nutrient status of a cell and sets of growth decision signaling based on its input. Several early PI3 kinase inhibitors, in fact, were later found to be dual PI3kinase inhibitors because not only are the two kinases’ signaling pathways similar –their kinase domains are, too.
July 25, 2014 / Blog
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