RIP kinase Inhibitor

GSK2983559 is an orally active and potent receptor interacting protein 2 (RIP2) kinase inhibitor. GSK2983559 blocks many proinflammatory cytokine responses in vivo and in human inflammatory bowel disease explant samples.

GSK547 (GSK'547) is a highly selective and potent inhibitor of receptor-interacting serine/threonine protein kinase 1 (RIPK1), inhibits macrophage-mediated adaptive immune tolerance in pancreatic cancer.

Eclitasertib (DNL-758) is a potent receptor-interacting protein kinase 1 (RIPK1) inhibitor with an IC₅₀ of 0.0375 µΜ.

RIPK-IN-4 is a selective RIPK2 inhibitor with an IC₅₀ value of 3 nM. RIPK-IN-4 can be used for the research of inflammatory diseases.

Oditrasertib (SAR443820) is an orally active, BBB-penetrable and selective reversible inhibitor of RIPK1. Oditrasertib can be used in the research of chronic inflammatory central nervous system diseases, such as amyotrophic lateral sclerosis and multiple sclerosis.

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

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.

Aurantiamide is a non-covalent, orally active, blood-brain-permeable GRPR selective antagonist with anti-inflammatory and neuroprotective effects. Aurantiamide reduces inflammation and oxidative stress in renal tissue by inhibiting GRPR-mediated renal necrosis pathways (such as RIPK3/MLKL signaling) and NF-κB inflammatory pathways, exerting anti-acute kidney injury and endothelial function activities. Aurantiamide also inhibits the M1 polarization of microglia and inhibits NLRP3 activation, thereby improving AD mouse models. Aurantiamide has in vivo inhibitory efficacy in acute kidney injury models such as ischemia/reperfusion, sepsis, and hypertension models.

Ligustroflavone is an orally active flavonoid compound. Ligustroflavone can be extracted from Ligustrum lucidum. Ligustroflavone antagonizes the calcium-sensing receptor (CaSR), inhibits the RIPK1/RIPK3/MLKL pathway, and downregulates TGF-β/Smad signaling. Ligustroflavone regulates calcium metabolism, protects bone tissue, reduces cerebral ischemic injury, and inhibits liver fibrosis. Ligustroflavone can be used in the study of diabetic osteoporosis, ischemic stroke, and liver fibrosis.

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

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.

Ocadusertib is a potent Serine/Threonine kinase receptor-interacting protein kinase 1 (RIPK1) inhibitor.

RIPK2-IN-5 (compound 14) is a high affinity and excellent selectivity RIPK2 inhibitor with an IC₅₀ value of 5.1nM. RIPK2-IN-5 has cellular anti-inflammatory effect and can reduce the secretion of MDP-induced TNF-α with a dose-dependent manner. RIPK2-IN-5 shows moderate stability in human liver microsome. RIPK2-IN-5 can be used for the research of immune diseases.

RIPK1-IN-7 is a potent and selective RIPK1 inhibitor with a K_d 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.

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

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.

GSK481 is a highly potent, selective, and specific receptor interacting protein 1 (RIP1) kinase inhibitor with an IC₅₀ of 1.3 nM, which inhibits Ser¹⁶⁶ phosphorylation in wild-type human RIP1 (IC₅₀=2.8 nM). GSK481 also exhibits excellent translation in the U937 cellular assay with an IC₅₀ of 10 nM.

PK68 is a potent orally active and specifical type II inhibitor of receptor-interacting kinase 1 (RIPK1) with an IC₅₀ of ~90 nM, displays inhibition of RIPK1-dependent necroptosis. PK68 powerfully ameliorates TNF-induced systemic inflammatory response syndrome, and can be used for the research of inflammatory disorders and cancer metastasis.

ZB-R-55 is an orally active and selective dual-mode RIPK1 inhibitor with RIPK1 IC₅₀ values of 5.7 nM. ZB-R-55 occupies both the allosteric and ATP binding sites of RIPK1. ZB-R-55 inhibits necroptosis in cancer cells. ZB-R-55 can be used for the research of systemic inflammatory response syndrome and sepsis.