Table 2 Classification of small molecule kinase inhibitors
From: Kinase-targeted cancer therapies: progress, challenges and future directions
Class of Kinase Inhibitor | Mechanism of Action | Examples |
|---|---|---|
Type I | Competes for the substrate and binds in the ATP-binding pocket of the active conformation | Bosutinib, Cabozantinib, Ceritinib, Crizotinib, Gefitinib, Pazopanib, Ruxolitinib, Vandetanib |
Type II | Type II inhibitors bind to the DFG-Asp out protein kinase conformation, which corresponds to an inactive enzyme form | Imatinib, Sorafenib, Axitinib, Nilotinib |
Type III (Allosteric Inhibitor) | Occupy a site next to the ATP-binding pocket so that both ATP and the allosteric inhibitor can bind simultaneously to the protein. | Trametinib, GnF2 |
Type IV (Substrate Directed Inhibitors) | Undergo a reversible interaction outside the ATP pocket and offer selectivity against targeted kinases | ONO12380 |
Type V (Covalent Inhibitor) | Bind covalently (irreversible)to their protein kinase target | Afatinib, Ibrutinib, HK1–272 |