A potent, selective, orally available RIPK2 inhibitor with IC50 of 3 nM.

GSK2982772 is a potent and ATP competitive RIP1 inhibitor with an IC50 of 16 nM.

GSK2983559 active metabolite is an active metabolite of GSK2983559. GSK2983559 active metabolite is a receptor interacting protein-2 (RIP2) kinase inhibitor extracted from patent WO/2014043446 A1, compound example 1.

GSK583 is a Highly Potent and Selective Inhibitor of RIP2 Kinase (RIP2K bing IC50=5 nM; rat in vivo PD IC50 = 50 nM).

GSK-872 is a potent and selective RIPK3 (receptor-interacting protein kinase-3) inhibitor.

HS-1371 is a novel kinase inhibitor of RIP3-mediated necroptosis.

RIPA-56 is a highly potent, selective, and metabolically stable inhibitor of receptor-interacting protein 1 (RIP1) with an IC50 of 13 nM.

WEHI-345 is a potent and selective inhibitor of RIPK2, with IC50 of 0.13 μM.

RIP2 kinase inhibitor 1 (compound 11) is a potent and selective receptor interacting protein 2 (RIP2) kinase inhibitor with an IC50 of 0.03 μM for RIP2 FP. RIP2 kinase inhibitor 1 is used for autoinflammatory disorders.

Necroptosis-IN-1, an analog of Necrostatin-1, is a potent necroptosi inhibitor. Necroptosis-IN-1 is a RIPK inhibitor.

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.

ICCB-19 hydrochloride is an inhibitor of TNFRSF1A Associated Via Death Domain (TRADD) with IC50 of 1.12 μM and 2.01 μM for protecting Velcade-induced apoptosis in Jurkat cells and protecting RDA in MEFs, respectively. ICCB-19 indirectly inhibits Receptor-interacting serine/threonine-protein kinase 1 (RIPK1). ICCB-19 effectively induces autophagy.

Eclitasertib (DNL-758) is a potent receptor-interacting protein kinase 1 (RIPK1) inhibitor with an IC50 of <1 µΜ (From patent WO2017136727A2, example 42).

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.

RIP2 Kinase Inhibitor 4 is a potent and selective RIPK2 PROTAC. RIP2 Kinase Inhibitor 4 effectively degrades RIPK2 (pIC50 of 8) and inhibits the release of related TNF-α.

RIPK1-IN-12 is a potent RIPK1 inhibitor. RIPK1-IN-12 inhibits necroptosis in both human and mouse cells, with EC50 values of 1.6 and 2.9 nM, respectively.

RIPK1-IN-11 is a potent and orally active RIPK1 inhibitor (Kd=9.2 nM; IC50=67 nM). RIPK1-IN-11 inhibits necroptosis in both human and mouse cells (EC50=17-30 nM). Anti-inflammatory activity.

RIPK1-IN-10 is a potent RIPK1 inhibitor, example 37, extracted from patent WO2021160109.

GW440139B is a potent RIPK3 inhibitor, suppresses necroptosis driven by dimerizable RIPK3 with IC50 of 73.6 nM.GW440139B inhibits TNF- and TRIF-mediated necroptosis independent of RIPK1-RIPK3 interaction, directly inhibited RIPK3-mediated MLKL phosphorylation at Ser345, thus inhibiting necroptosis.

Nigratine (6E11) is a highly specific, non-ATP competitive inhibitor of RIPK1 kinase (IC50=1.6 uM), inhibits necroptosis and ferroptosis.Nigratine inhibits necroptotic cell-death induced by TNF-α in Jurkat-Fadd def cells with IC50 of 4.6 uM.Nigratine is significantly more potent than the specific RIPK1 necroptosis inhibitor, Nec-1s.Nigratine (50 uM) strongly inhibits the ferroptotic cell death induced by excess of glutamate, erastin, and RSL3, in both murine HT22 and human SH-SY5Y cell lines, protects SH-SY5Y human neuroblastoma cell line from cell death triggered by both class I and II-inducers of ferroptosis.Nigratine protects porcine kidney epithelial LLC-PK1 cell line from lipid peroxidation and cell death triggered by RSL3.Nigratine protects human bronchial organoids from necroptosis and ferroptosis.

PK68 (RIPK1 inhibitor PK68) is a potent necroptosis inhibitor seletively targeting RIPK1 kinase activity, potently inhibits TNF-induced necroptosis (EC50, 23 and 13 nM in human and mouse cells, respectively).PK68 blocks cellular activation of RIPK1, RIPK3, and MLKL upon necroptotic stimuli.PK68 is a type II inhibitor of RIP1 kinase, highly selective inhibitor of RIPK1 kinase activity with IC50 of 90 nM, does not affect RIPK3 kinase activity at 1 uM, also demonstrated a reasonable selectivity against a panel of 369 kinases.PK68 exhibits a favorable pharmacokinetic profile and no obvious toxicity in mice.PK68 ameliorates TNF-induced systemic inflammatory response syndrome, and displays preventive suppression of tumor metastasis in the mouse cancer models.

SN-6109 (SN6109) is a small molecule inhibitor RIPK-1 with IC50 of 0.45 uM in radiometric kinase assays.SN-6109 reduced MLKL activation EC50 2.5-11.5 uM under long-term necroptosis execution in murine fibroblast L929 cells, and full protection from ATP depletion and membrane leakage in human and murine cells.SN-6109 decreased p-MLKL/MLKL and p-RIPK3/RIPK3 ratios in mouse liver tissue, showed efficacy in an in vivo model of tissue injury and inflammation driven by RIPK1/3-dependent cell death.