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.

ZB-R-55 is a potent and selective RIPK1 inhibitor with IC50 of 5.7 nM, 10-fold more potent than GSK2982772.ZB-R-55 is a dual-mode RIPK1 inhibitors occupying both the allosteric and the ATP binding pockets.ZB-R-55 exhibits excellent kinase selectivity, good oral pharmacokinetics and good therapeutic effects in the LPS-induced sepsis model.

ZJU-37 is a novel small molecule, BBB penetrant RIPK1 kinase inhibitor (IC50=366.4 nM) with higher potency than Nec-1s, prevents TNFα-induced necroptosis of Jurkat FADD−/− cells with IC50 of 185.2 nM.ZJU-37 promotes oligodendrocyte progenitor cells (OPCs) proliferation in vitro with higher efficacy than Nec-1s, enhances remyelination in vivo.ZJU-37 promotes transcription of PDGFRα and proliferation of OPCs via NF-κB.

OD36hydrochloride is a RIPK2 inhibitor with an IC50 of 5.3 nM. OD36 hydrochloride is a macrocyclic inhibitor with potent binding to the ALK2 kinase ATP pocket. OD36 hydrochloride shows ALK2-directed activity with KDs of 37 nM.

TP-030-1 is an inhibitor of RIPK1. TP-030-1 inhibits hRIPK1 with a Ki value of 3.9 nM and inhibits mRIPK1 with an IC50 value of 4.2 μM. TP-030-1 can be used for the research of inflammatory diseases and neurodegenerative diseases.

TP-030-2 is a RIPK1 inhibitor (human Ki=0.43 nM; mouse IC50=100 nM).

RI-962 is a potent and selective receptor-interacting protein kinase 1 (RIPK1) inhibitor. RI-962 inhibits RIPK1 with an IC50 value of 35.0 nM. RI-962 can be used for the research of nervous system diseases and inflammatory diseases.

SZM679 is a potent, orally active and selective RIPK1 inhibitor with Kd 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).

AC-003 is a novel oral small-molecule inhibitor of receptor interacting protein kinase 1(RIPK1) and has the potential for treating idiopathic pulmonary fibrosis.

aYM155 is a brain-penetrating prodrug form of YM155 (Cat. PC-42439, potent survivin inhibitor), displays potent cell killing activity against a broad panel of patient-derived GBM cancer stem-like cells (IC50=0.7-10 nM).

cRIPGBM (RIPGBM derivative cRIPGBM, RIPGBM-18) is a metabolite of RIPGBM induces apoptosis in GBM CSCs (EC50=68 nM in GBM 1 cells) by interacting with RIPK2 (Kd=2.3 uM).

Flizasertib is a potent, selective RIP1 kinase (RIPK1) inhibitor with potential for treating prophylaxis.

GNE-684 is a potent, cross-species, specific RIP1 kinase (RIPK1) inhibitor with IC50 of 21, 189 and 691 nM for human, mouse and rat RIP1, respectively.

GSK2593074A (GSK'074, GSK-2593074A) is novel potent, selective RIP1/RIP3 kinase dual inhibitor, directly binds to RIP1 and RIP3 with Kd of 130 and 12 nM, respectively.

Oditrasertib is a potent, selective RIPK1 inhibitor.

Zharp1-211 is a potent, selective, type II inhibitor of RIPK1 kinase with IC50 of 53 nM and binding Kd of 8.7 nM.

Zharp2-1 is a novel potent, selective RIPK2 inhibitor with IC50 of 38.5 nM in ADP-Glo kinase assay, effectively blocks RIPK2 kinase function and NOD-mediated NF-κB/MAPK activation.