| GSK′772 |
RIPK1 |
√ cellular (primate)
necroptosis assays |
GSK′772 is highly
potent and selective
for RIPK1, with extensive characterization in PK/PD and preclinical
models. It is unsuitable for use in nonprimate cells and in
vivo models due to excessive primate selectivity |
(120) |
| √ biochemical assays |
| √ in vitro primary cell (primate) assays |
| GNE684 |
RIPK1 |
√ cellular necroptosis assays |
GNE684 is highly potent and selective for RIPK1,
with similar levels of activity against primate and rodent orthologues.
Due to some limitations with the PK/PD properties, GNE684 is more
suitable for acute models of disease. |
(35) |
| √ biochemical assays |
| √ in vitro primary cell (primate) assays |
| √ in vivo models of necroptotic
disease |
| GSK′840 |
RIPK3 |
√ cellular necroptosis
assays |
GSK′840 is more potent and
selective for
RIPK3 than GSK′872 or GSK′843 but is only active against
primate RIPK3. |
(68) |
| √ biochemical
assays |
| √ in vitro primary cell (primate) assays |
| GSK′872 |
RIPK3 |
√ cellular necroptosis
assays |
GSK′872 is active against
both primate
and rodent RIPK3. Caution must be taken when used in vivo, as toxicity can occur at concentrations >1 μM. |
(3) |
| √ biochemical assays |
| √ in vitro primary cell (primate) assays |
| √ in vivo models of necroptotic
disease |
| NSA |
MLKL |
√ cellular (primate)
necroptosis assays |
NSA can only bind and
inhibit primate MLKL and
not rodent orthologues. Its use should be limited to in vitro assays. It is important to note that additional studies have also
linked NSA to pyroptosis. |
(54, 164, 165) |
| √ biochemical assays |
| √ in vitro primary cell (primate) assays |
