Enjoyed reading the latest publication from Novartis on ABL001 – a direct descendant of the GNF-2 and GNF-5 allosteric ABL inhibitors (https://www.nature.com/nature/journal/v543/n7647/full/nature21702.html). This class of compounds binds to the myristoyl binding pocket to disrupt kinase function. Intriguing aside were the effects that ABL001 had on the activity of ATP mimetics including Imatinib and Nilotinib (you may know the former as Gleevec). We have a long standing fascination with modified protein structures – we have seen first-hand how various activating fusion partners alter kinase biology (a story we are preparing for publication – hopefully). Reminds us how important adaptive protein structure is to function. Another great example is IL-2 binding to the alpha chain of the receptor – this triggers a conformational change in the IL-2 ligand that allows it to bind to the beta chain and ultimately form a tetrameric complex. Harness the power of the cell!