RIPK3 Inhibitor

GSK-872 is a RIPK3 inhibitor, which binds RIP3 kinase domain with an IC₅₀ of 1.8 nM, and inhibits kinase activity with an IC₅₀ of 1.3 nM. GSK-872 decreases the RIPK3-mediated necroptosis and subsequent cytoplasmic translocation and expression of HMGB1, as well as ameliorates brain edema and neurological deficits in early brain injury.

GSK-872 hydrochloride is a RIPK3 inhibitor, which binds RIP3 kinase domain with an IC₅₀ of 1.8 nM, and inhibits kinase activity with an IC₅₀ of 1.3 nM. GSK-872 hydrochloride decreases the RIPK3-mediated necroptosis and subsequent cytoplasmic translocation and expression of HMGB1, as well as ameliorates brain edema and neurological deficits in early brain injury.

UH15-38 is a potent RIPK3 inhibitor with an IC₅₀ value of 20 nM. UH15-38 blocks IAV (influenza A virus)-activated necroptosis. UH15-38 dampens IAV-induced lung injury.

GSK840 (GSK'840) is a receptor-interacting protein kinase 3 (RIP3 or RIPK3) inhibitor, which binds RIP3 kinase domain with an IC₅₀ of 0.9 nM, and inhibits kinase activity with an IC₅₀ of 0.3 nM.

GSK-843 (GSK'843) is a receptor-interacting protein kinase 3 (RIP3 or RIPK3) inhibitor, which binds RIP3 kinase domain with an IC₅₀ of 8.6 nM, and inhibits kinase activity with an IC₅₀ of 6.5 nM. GSK-843 can be used for the research of inflammation.

RIPK1/RIPK3-PPI-IN-1 is an orally active dual-target inhibitor of RIPK1/RIPK3, with a K_d value of 2.4 nM for RIPK1 and 24 nM for RIPK3. RIPK1/RIPK3-PPI-IN-1 inhibits the phosphorylation of RIPK1, RIPK3 and MLKL, thereby suppressing necroptosis. RIPK1/RIPK3-PPI-IN-1 restores body temperature, improves survival rate, and reduces IL-1β/IL-6 levels in serum and multiple organs of Mus musculus, thus alleviating TNF-α-induced systemic inflammatory response syndrome. RIPK1/RIPK3-PPI-IN-1 can be used in research related to systemic inflammatory response syndrome.

LT-1339-553 is a selective, orally active RIPK1 inhibitor with IC₅₀ values of 4.32, 95.74 and 84.33 nM against RIPK1, RIPK2 and RIPK3, respectively. LT-1339-553 exerts anti-necroptotic activity by inhibiting the AKT/PI3K/NF-κB pathway and the IL-17 pathway. LT-1339-553 reduces liver injury, inflammatory responses and collagen deposition. LT-1339-553 can be used in studies related to schistosomiasis-induced liver fibrosis.

UH15-38 TFA is a potent RIPK3 inhibitor with an IC₅₀ value of 20 nM. UH15-38 TFA blocks IAV (influenza A virus)-activated necroptosis. UH15-38 TFA dampens IAV-induced lung injury.

Aurantiamide is a non-covalent, orally active, blood-brain-permeable GRPR selective antagonist with anti-inflammatory and neuroprotective effects. Aurantiamide reduces inflammation and oxidative stress in renal tissue by inhibiting GRPR-mediated renal necrosis pathways (such as RIPK3/MLKL signaling) and NF-κB inflammatory pathways, exerting anti-acute kidney injury and endothelial function activities. Aurantiamide also inhibits the M1 polarization of microglia and inhibits NLRP3 activation, thereby improving AD mouse models. Aurantiamide has in vivo inhibitory efficacy in acute kidney injury models such as ischemia/reperfusion, sepsis, and hypertension models.

Ligustroflavone is an orally active flavonoid compound. Ligustroflavone can be extracted from Ligustrum lucidum. Ligustroflavone antagonizes the calcium-sensing receptor (CaSR), inhibits the RIPK1/RIPK3/MLKL pathway, and downregulates TGF-β/Smad signaling. Ligustroflavone regulates calcium metabolism, protects bone tissue, reduces cerebral ischemic injury, and inhibits liver fibrosis. Ligustroflavone can be used in the study of diabetic osteoporosis, ischemic stroke, and liver fibrosis.

RIPK3-IN-1 is a RIPK3 type II DFG-out inhibitor with an IC₅₀ of 9.1 nM. RIPK3-IN-1 inhibits RIPK1 and RIPK2 with IC₅₀s of 5.5 and >10 μM. RIPK3-IN-1 is also a c-Met kinase inhibitor with an IC₅₀ of 1.1 μM.

SZM679 is a potent, orally active and selective RIPK1 inhibitor with K_d values of 8.6 nM and >5000 nM for RIPK1 and RIPK3, respectively. SZM679 reverses the tumor necrosis factor-induced systemic inflammatory response. SZM679 decreases the Tau hyperphosphorylation, neuroinflammation, and the RIPK1 phosphorylation level in the hippocampus and cortex. SZM679 can be used in research of Alzheimer's disease (AD).

RIPK2/3-IN-2 (29) is a dual RIPK2 and RIPK3 inhibitor, with IC₅₀ values of 12 nM and 18 nM, respectively. RIPK2/3-IN-2 (29) induces necroptosis, with an EC₅₀ of 0.16 μM.

Zharp1-163 is a dual inhibitor of ferroptosis and necroptosis. Zharp1-163 effectively blocks ferroptosis by reducing reactive oxygen species (ROS) levels and inhibits necroptosis by potently and selectively targeting RIPK1 kinase activity (K_D = 240 nM; IC₅₀ = 406.1 nM). Zharp1-163 inhibits the cellular activation of RIPK1, RIPK3 and MLKL in response to necroptotic stimulation. Zharp1-163 markedly attenuates TNF-α (HY-P1875)-induced systemic inflammatory syndrome, including the prevention of TNF-α-induced mortality and hypothermia in mice. Zharp1-163 significantly alleviates acute kidney injury associated with both necroptosis and ferroptosis in models induced by Cisplatin (HY-17394) and ischemia-reperfusion. Zharp1-163 can be used for the study of diseases associated with cell death pathways, such as kidney disease.

SZM-1209 is an orally active, potent and specific RIPK1 inhibitor, with a K_d of 85 nM. SZM-1209 exhibits high anti-necroptotic activity (EC₅₀=22.4 ± 8.1 nM). SZM-1209 shows anti-SIRS (systemic inflammatory response syndrome), and anti-ALI (acute lung injury) effects.

RIPK3-IN-6 (compound 1) is a type I RIPK3 inhibitor with poor selectivity for the RIPK family, especially for RIPK2 activity.

RIPK2-IN-8 is an orally active and highly selective RIPK2 inhibitor (IC₅₀ = 11 nM). RIPK2-IN-8 is highly selective for RIPK2 over RIPK1 (IC₅₀ > 30,000 nM) and has a moderate inhibitory effect on RIPK3 (IC₅₀ = 44.61 nM). RIPK2-IN-8 inhibits the NOD2-RIPK2 signaling pathway and the expression of the inflammatory cytokines IL-6 and TNFα, thereby exerting anti-inflammatory effects. RIPK2-IN-8 has demonstrated anti-inflammatory and hepatoprotective effects in an acute liver injury (ALI) model and can be used in ALI research.

IL-6/RIPK3-IN-1 is an inhibitor of IL-6, RIPK3 and BRD4, with IC₅₀ values of 0.22, 1.32 and 5.91 μM, respectively. IL-6/RIPK3-IN-1 can be used in studies related to inflammation and tissue damage.

RIPK1-IN-39 (compound 2) is a potent and selective RIPK1 inhibitor (IC₅₀ = 69.40 nM) exhibiting >100-fold selectivity over RIPK3 (IC₅₀ = 6946 nM). RIPK1-IN-39 protects HT-22 and HT-29 cells from necroptosis by inhibiting the phosphorylation and activation of the RIPK1-RIPK3-MLKL pathway. RIPK1-IN-39 demonstrates neuroprotective effects in a rat model of middle cerebral artery occlusion (MCAO). RIPK1-IN-39 can be used for acute ischemic stroke (AIS) research.

WJH-C19 is an orally active RIPK1 inhibitor with an IC₅₀ of 5.7 nM. WJH-C19 inhibits the RIPK1/RIPK3/MLKL signaling axis, blocks RIPK1 phosphorylation, suppresses the phosphorylation of downstream RIPK3 and MLKL, disrupts necrosome formation, and exhibits protective effects against necroptosis (Apoptosis) in multiple cell lines. WJH-C19 ameliorates symptoms of inflammatory bowel disease in a mouse colitis model by regulating the necroptosis pathway. WJH-C19 alleviates inflammation and bone destruction in a mouse model of rheumatoid arthritis. WJH-C19 is applicable to research related to inflammatory bowel disease and rheumatoid arthritis.