RIP kinase Inhibitor

Necrostatin-1 (Nec-1) is a potent and cross the blood-brain barrier necroptosis inhibitor with an EC₅₀ of 490 nM in Jurkat cells. Necrostatin-1 inhibits RIP1 kinase (EC₅₀=182 nM). Necrostatin-1 is also an IDO 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.

Necrostatin 2 racemate (Nec-1S), the Necrostatin-1 (HY-15760) stable, is a potent and specific RIPK1 inhibitor lacking the IDO-targeting effect.

GSK583 is a highly potent, orally active and selective inhibitor of RIP2 Kinase, with IC₅₀ of 5 nM. GSK583 inhibits both TNF-α and IL-6 production with an IC₅₀ value of 200 nM.

RIPK3-IN-7 is a RIPK3 inhibitor that suppresses the RIPK3-mediated necroptosis pathway. RIPK3-IN-7 can be used for research on necroptosis and inflammation-related 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.

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.

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.

Primidone is the orally active inhibitor for TRPM3 (IC₅₀ = 0.6 μM), RIP kinase and voltage-gated sodium channel, and the antagonist for GABA receptor. Primidone can be used as the analgesic and anticonvulsant agent.

GLPG3312 (Compound 28) is an orally active SIK inhibitor with IC₅₀ values of 2.0 nM, 0.7 nM and 0.6 nM for SIK1, SIK2 and SIK3, respectively. GLPG3312 exhibits anti-inflammatory and immunomodulatory activity in vitro on human primary myeloid cells and in vivo in mouse models. GLPG3312 has good oral bioavailability and can be used for research on inflammatory and immune diseases.

GSK2982772 is a potent, orally active and ATP competitive RIP1 kinase inhibitor with IC₅₀ values of 16 nM and 20 nM for human and monkey RIP1, respectively.

Apostatin-1 (Apt-1) is a potent TRADD inhibitor. Apostatin-1 can bind with TRADD-N (K_D=2.17 μM), disrupting its binding to both TRADD-C and TRAF2. Apostatin-1 modulates the ubiquitination of RIPK1 and beclin 1. Apostatin-1 blocks apoptosis and restores cellular homeostasis by activating autophagy in cells with accumulated mutant tau, α-synuclein, or huntingtin.

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.

ICCB-19 hydrochloride is a TRADD (TNFRSF1A associated via death domain) inhibitor. ICCB-19 hydrochloride binds with N-terminal domain of TRADD (TRADD-N), disrupting its binding to both TRADD-C and TRAF2. ICCB-19 hydrochloride is indirect inhibitor of RIPK1 kinase activity. ICCB-19 hydrochloride effectively induces autophagy and the degradation of long-lived proteins.

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.

Necrostatin 2 is a potent necroptosis inhibitor. EC₅₀ for inhibition of necroptosis in FADD-deficient Jurkat T cells treated with TNF-α is 0.05 μM. Necrostatin 2 is also a RIPK1 inhibitor.

WEHI-345 is a potent and selective RIPK2 kinase inhibitor with an IC₅₀ of 0.13 μM, which delays RIPK2 ubiquitylation and NF-κB activation on oligomerization domain (NOD) stimulation.

RIPA-56 is a highly potent, selective, and metabolically stable inhibitor of receptor-interacting protein 1 (RIP1) with an IC₅₀ of 13 nM. RIPA-56 can be used for the treatment of systemic inflammatory response syndrome.

GSK963 is a chiral, highly potent and selective inhibitor of RIP1 kinase, with an IC₅₀ of 29 nM. GSK963 is a selective and potent inhibitor of necroptosis in murine and human cells in vitro.