Table 1.
Target proteins associated with necroptosis and their specific inhibitors
| Necroptosis Target proteins | Inhibitors | Mode of action/function |
|---|---|---|
| RIP-1 | Nec-1 | Allosteric inhibitor |
| Furo[2,3-d]pyrimidine derivatives | SAR reported | |
| GSK’963 | > 10000-fold selective for RIP1 | |
| RIP-3 | GSK’840, GSK’843, GSK’872 | Caspase activity activated |
| MLKL | Necrosulfonamide | Covalent binding |
| TC13172 | Covalent binding (nanomolar potency) | |
| GW806742X | Binds to pseudokinase domain (ATP-mimetic) | |
| Others | Ponatinib & pazopanib | Interfere with signaling proteins upstream of MLKL |
| Sorafenib | Target unknown | |
| TPCK | UCH-L1 activator | |
| Hydroxyanisole | ROS scavenger | |
| Diphenyleneiodonium (DPI) | ROS suppression |