RIP Kinase

RIPK1-IN-19 is a selective inhibitor of receptor-interacting protein kinase 1 (RIPK1), exhibiting an IC50 of 15 nM. It demonstrates significant protective effects in models of systemic inflammatory response syndrome (SIRS) induced by TNFα, as well as in imiquimod-induced psoriasis models. This compound serves as a valuable tool for investigating the roles of RIPK1 in inflammation and immune system disorders.

KWCN-41 is a selective inhibitor of RIPK1 kinase, exhibiting an IC50 value of 88 nM. This compound specifically targets and inhibits cell necrosis while leaving apoptotic pathways unaffected. Additionally, KWCN-41 demonstrates anti-inflammatory properties, making it a valuable tool for research in cell death mechanisms and inflammation-related studies.

RIPK1-IN-24 is a selective inhibitor of receptor-interacting protein kinase 1 (RIPK1) with an IC50 value of 1.3 μM. This compound is utilized in research investigating the role of RIPK1 in inflammatory diseases, making it a valuable tool for studies on cell survival, apoptosis, and signal transduction pathways. Researchers can leverage RIPK1-IN-24 to elucidate the mechanisms underlying inflammation-related pathologies and explore potential therapeutic strategies.

RIPK1-IN-35 is a selective and orally bioavailable inhibitor of receptor-interacting protein kinase 1 (RIPK1) with an IC50 of 5.33 nM. This compound exhibits a strong protective effect against necroptosis in both human and murine cell models. It demonstrates significant therapeutic potential in experimental models of TNF-α-induced systemic inflammatory response syndrome and DSS-induced inflammatory bowel disease. RIPK1-IN-35 is valuable for research into inflammatory diseases associated with necroptosis.

RIPK3-IN-2 is a selective inhibitor of receptor-interacting protein kinase 3 (RIPK3), which plays a crucial role in necroptotic cell death pathways. This compound is utilized in research focused on diseases associated with activated necroptosis, providing insights into the underlying mechanisms of cellular pathology and potential therapeutic interventions. Its ability to modulate RIPK3 activity makes it a valuable tool for studying necrotic processes in various biological contexts.

RIPK1-IN-8 is a selective inhibitor of receptor-interacting protein kinase 1 (RIPK1), exhibiting a potent inhibitory activity with an IC50 value of 4 nM. This compound is valuable for research into inflammatory diseases, providing insights into RIPK1-mediated signaling pathways and their role in inflammation and cell death. Its specificity and efficacy make it a suitable tool for investigating the therapeutic potential of RIPK1 inhibition in various disease models.

RIPK2-IN-6 is a selective inhibitor of RIPK2, effectively blocking its phosphorylation and subsequently inhibiting the NF-κB and MAPK signaling pathways. This compound exhibits significant anti-inflammatory and anti-fibrotic properties, demonstrated in Dextran sodium sulfate-induced colitis models in mice. RIPK2-IN-6 is valuable in research exploring therapeutic strategies for inflammatory and fibrotic diseases.

RIPK2-IN-5 is a high-affinity inhibitor of receptor-interacting protein kinase 2 (RIPK2), demonstrating an IC50 value of 5.1 nM. This compound exhibits significant anti-inflammatory effects by reducing the secretion of TNF-α in response to MDP in a dose-dependent manner. With moderate stability in human liver microsomes, RIPK2-IN-5 serves as a valuable tool for investigating immune diseases and related therapeutic strategies.

RIPK2-IN-7 is a potent and selective inhibitor of RIPK2, exhibiting an IC50 of 0.6 nM. This compound effectively inhibits RIPK2 kinase activity, thereby disrupting the nucleotide-binding oligomerization domain (NOD) signaling pathway and decreasing the production of pro-inflammatory cytokines such as TNFα. RIPK2-IN-7 is a valuable tool for researching inflammatory bowel disease (IBD) and related inflammatory conditions.

RIPK1-IN-36 is a potent inhibitor of receptor-interacting protein kinase 1 (RIPK1) with an EC50 of less than 25 nM. This compound is valuable for investigating the role of RIPK1 in various pathological conditions, including inflammatory diseases and neurodegenerative disorders. Researchers can utilize RIPK1-IN-36 to explore the therapeutic potential of targeting RIPK1 signaling pathways in relevant biological models.

CSLP43 is a selective inhibitor of RIPK2, demonstrating an IC50 of 19.9 nM against human RIPK2. By binding to the ATP-binding pocket of RIPK2, CSLP43 disrupts its interaction with the BIR2 domain of XIAP and cIAP1, effectively inhibiting RIPK2 ubiquitination and regulating NOD1- and NOD2-dependent inflammatory signaling pathways, as well as NF-κB activation. This compound is particularly relevant for research investigating Crohn's disease, Blau syndrome, early-onset sarcoidosis, and early-onset inflammatory bowel disease, due to its selectivity for the NOD1/NOD2 signaling pathway without affecting RIPK1 or RIPK3 activity.

RIPK2/3-IN-2 is a potent dual inhibitor of receptor-interacting protein kinases 2 and 3 (RIPK2 and RIPK3), exhibiting IC50 values of 12 nM and 18 nM, respectively. This compound effectively induces necroptosis, showcasing an EC50 value of 0.16 μM. RIPK2/3-IN-2 can be utilized in research exploring programmed cell death mechanisms and the role of necroptosis in various pathological conditions.

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

GSK481 is a novel benzoxazepinone (BOAz) series of RIP1 inhibitors. Receptor Interacting Protein Kinase 1 (RIP1) has been implicated as a key contributor to inflammation through the regulation of programmed necrosis. Inhibition of this kinase has been shown to hinder cell necrotic death, thereby establishing RIP1 as a viable target for the potential treatment of multiple inflammatory diseases.

GSK2593074A (GSK??074) is a necroptosis inhibitor with dual targeting ability to both RIP1 and RIP3.

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.

GSK583 is a highly potent and selective inhibitor of RIP2 Kinase.

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

RIP2 kinase inhibitor 2 is a receptor interacting protein-2 (RIP2) kinase inhibitor extracted from patent WO/2014043437 A1, compound example 9.

GSK2983559 free acid (compound 3) is a potent, specific and oral bioavailable receptor interacting protein 2 (RIP2) kinase 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.

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.

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.

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.

RIP2 Kinase Inhibitor 3 is a highly potent and selective inhibitor of receptor interacting protein-2 (RIP2) Kinase with an IC50 of 1 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.

PK68 is a potent and selective type II inhibitor of receptor-interacting kinase 1 (RIPK1) with an IC50 of ~90?nM, displays inhibition of RIPK1-dependent necroptosis.

HS-1371 is a potent and ATP-competitive receptor-interacting protein kinase 3 (RIP3) inhibitor with an IC50 of 20.8?nM.

RIPK1-IN-7 is a potent and selective 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.

RIPK1-IN-3 (Example 38), a RIPK1 inhibitor, extracted from patent WO2018148626A1, possesses anti-inflammatory proprieties.

GSK547 (GSK-547) is a highly selective and potent inhibitor of receptor-interacting serine/threonine protein kinase 1 (RIP1), inhibits macrophage-mediated adaptive immune tolerance in pancreatic cancer.

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.

GSK3145095 is a RIP1 kinase inhibitor with an IC50 of 6.3 nM .

RIPK-IN-4 is a potent and selective RIPK2 inhibitor with excellent oral bioavailability, and has an IC50 of 3 nM.