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].
RIPK2 inhibitor 1 is a novel potent, selective RIPK2 inhibitor with IC50 of 5-10 nM; potently inhibits the proliferation of cancer cells by > 70% and also inhibits NF-κB activity.
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].
RIPK3-IN-2 is a RIP3 inhibitor. RIPK3-IN-2 can be used in diseases caused by or associate with activated necrotic pathways research[1].
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.
Oditrasertib is a RIPKl inhibitor with an IC50 value lower than 100 nM. Oditrasertib can be used for the research of Inflammation[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.
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[1].
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].
RIP1 kinase inhibitor 1 (compound 22) is a highly potent, orally available, and brain-penetrating RIP1 kinase inhibitor (pKi=9.04)[1].
GSK'481 can inhibit RIP1 WT S166 phosphorylation in human vs mouse plasmids overexpressed in HEK293T cellsGSK'481 have approximately equivalent RIP1 FP potencies against human andcynomolgus monkey RIP1 but was >100-fold less potent against nonprimate RIP1
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].
GSK3145095 is a RIP1 kinase inhibitor with an IC50 of 6.3 nM [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-15 (Compound 2.5) is a potent inhibitor of RIPK1. RIPK1-IN-15 has the potential for the research neurodegenerative, autoimmune, and inflammatory 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].
Kongensin A is a natural product isolated from Croton kongensis. Kongensin A is an effective, covalent HSP90 inhibitor that blocks RIP3-dependent necroptosishas. Kongensin A is a potent necroptosis inhibitor and an apoptosis inducer. Kongensin A has potential anti-necroptosis and anti-inflammation applications[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].
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].
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].
RIP2 Kinase Inhibitor 3 is a highly potent and selective inhibitor of receptor interacting protein-2 (RIP2) Kinase with an IC50 of 1 nM [1].
RIPK2-IN-1 (compound 18f) is a potent RIPK2 inhibitor with an IC50 of 51 nM. RIPK2-IN-1 inhibits ALK2 with an IC50 of 5 nM. RIPK2-IN-1 has an IC50 of 390 nM on RIPK2/NOD2 in cell assay[1].
Eclitasertib (DNL-758) is a potent receptor-interacting protein kinase 1 (RIPK1) inhibitor with an IC50 of <1 µΜ (From patent WO2017136727A2, example 42)[1].
GSK547, a highly selective and potent RIP1 inhibitor, inhibits macrophage-mediated adaptive immune tolerance in pancreatic cancer[1].
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[1][2].
GSK2982772 is a potent and ATP competitive RIP1 inhibitor with an IC50 of 16 nM.
RIP1 kinase inhibitor 8 (Compound 77) is a potent and highly selective dihydropyrazole (DHP) RIP1 kinase inhibitor with an IC50 of 20 nM. RIP1 kinase inhibitor 8 prevents necrotic cell death. RIP1 kinase inhibitor 8 shows a favorable pharmacokinetic profile in multiple species[1].