RIP kinase Inhibitor

Desmethyl-WEHI-345 analog is a protein kinase inhibitor extracted from patent WO2012003544A1, example 12. Desmethyl-WEHI-345 analog can be used for the research of colon cancer.

RIPK1-IN-25 (WL8) is a blood-brain permeable RIPK1 inhibitor with EC₅₀ and K_d values are 19.9 and 25 nM, respectively. RIPK1-IN-25 can be used in the study of neurometabolic diseases.

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.

RIP1 kinase inhibitor 5 (example 1) is a potent inhibitor of RIP1, which is used as a checkpoint kinase to control tumor immunity. RIP1 kinase inhibitor 5 is similar with SIR1-365 (compound 13), which inhibits necrosis and iron death activity.

RIPK1-IN-9 (example 45), a dihydronaphthyridone compound, is a potent and selective RIPK1 inhibitor. RIPK1-IN-9 inhibits U937 cell (IC₅₀=2 nM) and L929 cell (IC₅₀=1.3 nM).

RIPK1-IN-20 (compound 13c) has a favorable RIPK1 kinase inhibition activity with an IC₅₀ value of 59.8 nM. RIPK1-IN-20 blocks TNFα-induced necroptosis in both human and murine cells (EC₅₀=1.06–4.58 nM).

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.

RIPK1-IN-16 is an orally active and potent inhibitor of RIPK1. RIPK1-IN-16 inhibits excessive inflammation by blocking RIPK1-mediated necroptosis in vivo. RIPK1-IN-16 protects mouse from TNF-induced systemic inflammatory response syndrome and sepsis.

RIPK3-IN-5 (compound 32) is a potent RIPK3 inhibitor with an IC₅₀ of 27 nM. RIPK3-IN-5 also inhibits necroptosis with an EC₅₀ of 0.45 μM.

RIPK1-IN-34 is a selective, brain-penetrant RIPK1 inhibitor (IC₅₀ = 126.70 nM) with almost no inhibitory effect on RIPK3 (IC₅₀ ＞ 10, 000 nM). RIPK1-IN-34 offers substantial neuroprotection by inhibiting the phosphorylation of RIPK1, RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) within the necroptosis pathway. RIPK1-IN-34 shows the neuroprotective effect in a rat middle cerebral artery occlusion (MCAO) model. RIPK1-IN-34 can be used for the study of anti-acute ischemic stroke (AIS).

RIPK1-IN-37 is an RIPK1 inhibitor and a ligand for the target protein for PROTAC LD5097 (HY-179234). RIPK1-IN-37 can be used to synthesize PROTAC.

Tat-ASIC1a (1-20) (mouse, rat) is a competitive ASIC1a membrane-penetrating peptide. Tat-ASIC1a (1-20) (mouse, rat) has significantly neuroprotection effects, and reduces neuronal damage against acidotoxicity by targeting the ASIC1a-RIPK1 pathway and auto-inhibitory mechanism. Tat-ASIC1a (1-20) (mouse, rat) effectively protects brains from ischemic injury in ischemic stroke mice model. Tat-ASIC1a (1-20) (mouse, rat) can be used for neurodegenerative diseases research, such as Huntington disease and Parkinson’s disease.

Ripk2 Mouse Pre-designed siRNA Set A contains three designed siRNAs for Ripk2 gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.

RIPK1-IN-18 (compound i) is a potent inhibitor of RIPK1. RIPK1-IN-18 can be used in autoimmune diseases research.

RIPK1-IN-13 (Compound 8) is a potent inhibitor of RIPK1 with an IC₅₀ value of 1139 nM. RIPK1-IN-13 blocks the activation of the necroptosis pathway via the inhibition of RIPK1. RIPK1-IN-13 has the potential for the research of inflammation diseases.

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.

NOD1/2-IN-1 (Compound 18) is a potent RIPK2 inhibitor with an IC₅₀ value of 1.4 nM, as determined by the ADP-Glo assay. NOD1/2-IN-1 blocks the production of pro-inflammatory cytokines by inhibiting the NOD1/NOD2 pathways, with IC₅₀ values of 18 nM and 170 nM for NOD1 and NOD2, respectively, thereby reducing inflammatory responses. NOD1/2-IN-1 can be used in studies related to colitis.

VWK147 is a second-generation HSP90 C-terminal domain (CTD) inhibitor. VWK147 targets the CTD dimerization interface, prevents HSP90 CTD dimerization, disrupts co-chaperone PPID binding to HSP90 CTD, and inhibits HSP90 chaperone function dependent on dimerization. VWK147 reduces protein levels of HSP90 client proteins ULK1, RIPK1, and CDK4 without inducing a heat shock response. VWK147 induces cell death, including apoptosis, in Cisplatin (HY-17394)-sensitive and -resistant urothelial carcinoma cells. VWK147 induces LC3-II accumulation, inhibits autophagosome-lysosome fusion to block canonical autophagy, and induces non-canonical LC3 lipidation independent of ULK1 and PIK3C3 complexes. VWK147 can be used for the research of urothelial carcinoma.

RIPK1-IN-43 is a triazolopyridine compound and also a RIPK1 inhibitor. RIPK1-IN-43 can be used in the research of diseases associated with abnormal RIPK1, such as multiple sclerosis, Parkinson's disease, non-alcoholic steatohepatitis, etc.

RIPK1-IN-38 is an orally active RIPK1 inhibitor with an IC₅₀ value of 27 nM. RIPK1-IN-38 can inhibit the phosphorylation of RIPK1 and its downstream signaling molecules RIPK3 and MLKL. RIPK1-IN-38 exhibits anti-necroptotic activity. RIPK1-IN-38 has excellent anti-inflammatory efficacy in both the SIRS model and GVHD model. RIPK1-IN-38 can be used for the research of inflammatory and immune-related diseases.