Binding of the ITD-altered FLT3 tyrosine kinase receptor by type I and type II TKIs. (A) Type II inhibitors are thought to bind the inactive conformation of the FLT3 receptor tyrosine kinase and in this manner potently inhibit the ITD-altered FLT3 tyrosine kinase, but they have limited activity against secondary point mutations such as D835, because (B) D835 point mutations are thought to destabilize the inactive conformation of the FLT3 kinase in favor of the active conformation. Therefore, type I inhibitors, such as crenolanib, which can also bind the active conformation of the enzyme, can effectively inhibit the FLT3 kinase altered by the D835 mutation. FL, FLT3 ligand. Professional illustration by Alice Y. Chen.