Table 1.

Current classification of TKIs

Class	Binding	ATP-competitive	Reversible binding	Examples of FDA approved TKIs
Type I	In the ATP-binding pocket of the active enzyme conformation	Yes	Yes	Cabozantinib, Dasatinib, Erlotinib, Gefitinib, Vandetanib,
Type I ½ A	In the ATP-binding pocket of a conformation with DFG-Asp in and αC-helix out with extension to back cleft of the ATP site	Yes	Yes	Lenvatinib, Lapatinib
Type I ½ B	In the ATP-binding pocket of a conformation with DFG-Asp in and αC-helix out without extension to back cleft of the ATP site	Yes	Yes	Alectinib, Ceritinib, Crizotinib, Erlotinib
Type II A	In the ATP-binding pocket of a conformation with DFG-Asp out with extension to back cleft of the ATP site	Yes	Yes	Axitinib, Imatinib, Nilotinib, Ponatinib, Sorafenib
Type II B	In the ATP-binding pocket of a conformation with DFG-Asp out without extension to back cleft of the ATP site	Yes	Yes	Bosutinib, Sunitinib, Nintedanib
Type III	Allosterically next to but outside of ATP-binding site with the extension to back cleft of the ATP site	No	No	-
Type IV	Allosterically not next to the ATP-binding site	No	No	-
Type V	Bivalently to two regions of PK domain	Variable	Yes	-
Type VI	Covalently to Cys residues	No	Usually no	Afatinib, Ibrutinib