RIPK2/3-IN-1 is a potent inhibitor of both RIPK2 and RIPK3 kinases, exhibiting IC50 values of 3 nM for RIPK2 and 117 nM for RIPK3. Additionally, in a 14-TriLAN-Gly/NOD1 THP-1 cell-based NF-κB reporter assay, RIPK2/3-IN-1 demonstrates an IC50 value of 14 ± 4 nM against RIPK2 [1].

RIPK1/3-IN-1 (Compound 10) is a selective inhibitor of both RIPK1 and RIPK3, effectively preventing necroptosis by blocking the phosphorylation of RIPK1, RIPK3, and MLKL [1].

Necrostatin-5 (Nec-5) is a selective inhibitor of RIP1 kinase and a cell necrosis inhibitor that prevents the death of Fadd-deficient Jurkat cells treated with TNF-α with an EC50 value of 240 nM.

Eclitasertib is a potent inhibitor of receptor-interacting protein kinase 1 (RIPK1, IC50 of <1 µΜ).

SZM679 is an orally active, selective RIPK1 inhibitor displaying potent affinity with a dissociation constant (Kd) of 8.6 nM for RIPK1, while exhibiting minimal activity towards RIPK3, with a Kd of >5000 nM. It effectively counteracts tumor necrosis factor-induced systemic inflammation, reduces Tau hyperphosphorylation, diminishes neuroinflammation, and lowers RIPK1 phosphorylation in the hippocampus and cortex. SZM679 is utilized in Alzheimer’s disease (AD) research [1].