Nec-4, a tricyclic derivative, is a potent receptor interacting protein 1 (RIP1) inhibitor, with an IC50 of 2.6 μM, Ki of 0.46 μM.
RIP1 kinase inhibitor 6 is a potent and selective RIP1 kinase inhibitor with an IC50 of < 100 nM in human R1P1 kinase assay. RIP1 kinase inhibitor 6 is extracted from patent WO2020103884, example 80[1].
AV123 (compound 12) is a non-cytotoxic RIPK1 inhibitor (IC50=12.12 µM). AV123 blocks the TNF-α-induced necroptotic (EC50=1.7 μM) but not the apoptotic cell death. AV123 can be used in the study of necrotic chronic conditions such as ischemia-reperfusion injury of the brain, heart and kidney, inflammatory diseases, neurodegenerative diseases and infectious diseases[1].
RIPK1-IN-4 (compound 8) is a potent and selective type II kinase inhibitor of receptor interacting protein 1 (RIP1) kinase and binds to a DLG-out inactive form of RIP1 with an IC50s of 16 nM and 10 nM for RIP1 and ADP-Glo kinase[1].
Necrostatin-5 (Nec-5) is a potent necroptosis inhibitor with an EC50 value of 0.24 µM. Necrostatin-5 also is a RIP1 inhibitor. Necrostatin-5 shows cardioprotective effects[1][2][3].
Zharp2-1 is an oral effective RIPK2 inhibitor, highly associated with inflammatory bowel disease (IBD). Zharp2-1 blocker muramyl dipeptide (MDP) induces growth of mononuclear cells and induces inflammatory cell factor infection. Zharp2-1 attenuates MDP-induced small inguinal peritonitis, or ameliorates by DNBS-induced large inguinal conjunctivitis[1].
GSK2982772 is a potent and ATP competitive RIP1 inhibitor with an IC50 of 16 nM.
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[1].
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[1].
HS-1371 is a potent and ATP-competitive RIP3 inhibitor with an IC50 of 20.8 nM[1].
RIPK1-IN-3 (Example 38), a RIPK1 inhibitor, extracted from patent WO2018148626A1, possesses anti-inflammatory proprieties[1].
RIPK3-IN-4 (Compound 42) is a RIPK3 inhibitor. RIPK3-IN-4 inhibits HK-2 cell damage, necroptosis and inflammatory responses. RIPK3-IN-4 reduces Cisplatin (HY-17394)- and I/R-induced kidney damage, inflammatory response and necroptosis in acute kidney injury[1].
RIPK1-IN-7 is a potent and selective receptor-interacting protein kinase 1 (RIPK1) inhibitor with a Kd of 4 nM and an enzymatic IC50 of 11 nM. RIPK1-IN-7 exhibits excellent antimetastasis activity in the experimental B16 melanoma lung metastasis model[1].
cRIPGBM(chloride), an orally active, proapoptotic derivative. cRIPGBM can be generated from glioblastoma multiforme (GBM) cancer stem cells (CSCs). cRIPGBM(chloride) targets to receptor-interacting protein kinase 2 (RIPK2) to induce caspase 1-dependent apoptosis. cRIPGBM(chloride) suppresses the formation of RIPK2/TAK1 (prosurvival complex), and increases the formation of RIPK2/caspase 1 (proapoptotic complex). cRIPGBM(chloride) exerts potent anti-tumor activity in vivo in animal models[1].
TP-030-2 is a RIPK1 inhibitor (human Ki=0.43 nM; mouse IC50=100 nM)[1][2].
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)[1].
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.
GSK583 is a highly potent and selective inhibitor of RIP2 Kinase, with IC50 of 5 nM.
Apostatin-1 (Apt-1) is a potent TRADD inhibitor. Apostatin-1 can bind with TRADD-N (KD=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[1].
GSK3145095 is a RIP1 kinase inhibitor with an IC50 of 6.3 nM [1].
WEHI-345 is a potent and selective inhibitor of RIPK2, with IC50 of 0.13 μM.IC50 value: 0.13 μMTarget: RIPK2in vitro: WEHI-345 is a selective RIPK2 kinase inhibitor, which delays RIPK2 ubiquitylation and NF-κB activation downstream of NOD engagement. WEHI-345 is an ATP analogue and was therefore predicted to bind in the ATP-binding pocket of RIPK2. WEHI-345 proved to be highly specific for RIPK2(Kd=46 nM) and displayed negligible activity (>10 μM) against RIPK1, RIPK4 and RIPK5.in vivo: WEHI-345 inhibits NOD signalling and has a beneficial effect on an EAE model. WEHI-345 blocks MDP-induced cytokine production. WEHI-345 ameliorates experimental autoimmune encephalomyelitis in mice. WEHI-345 also potently inhibited MDP-induced cytokine and chemokine secretion in the mouse macrophage Raw 264.7 cell line.
RIPK2-IN-2 (example 25) is a RIP2 kinase PROTAC inhibitor. RIPK2-IN-2 can block RIP2-dependent proinflammatory signaling, regulated RIP2 kinase activity in auto inflammatory diseases[1].
HTH-01-091 is a potent and selective, cell-permeable, ATP-competitive MELK inhibitor with biochemical IC50 of 10.5 nM; displays no significant activity for PIK3CA, mTOR, GSK3A and CDK7 (IC50>600 nM); exhibits substantially improved kinome selectivity in comparison with OTSSP167; induces MELK degradation, but demonstrates poor antiproliferative effects in basal-like breast cancer cell lines.
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[1].
RIP2 kinase inhibitor 2 is a receptor interacting protein-2 (RIP2) kinase inhibitor extracted from patent WO/2014043437 A1, compound example 9.
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[1].
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[1].
PROTAC RIPK degrader-6 (example 1) is a PROTAC targeting RIP Kinase degradation wherein the RIP2 kinase inhibitor is linked via a linker to a cereblon binder[1].
Oditrasertib is a RIPKl inhibitor with an IC50 value lower than 100 nM. Oditrasertib can be used for the research of Inflammation[1].
RIP1 kinase inhibitor 1 (compound 22) is a highly potent, orally available, and brain-penetrating RIP1 kinase inhibitor (pKi=9.04)[1].