RIP kinase Inhibitor

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.

RIPK1-IN-21 (Compound I-5) is an inhibitor of RIPK1 with an EC₅₀ value of 14.8 nM. RIPK1-IN-21 can be used in the research of neurodegenerative, autoimmune, and inflammatory diseases.

(Neurodegenerative diseases) NDs-IN-1 (Compound 3g) inhibits the activities of key enzymes such as hBACE-1, hAChE and hMAO-B. NDs-IN-1 is a novel non-covalent multi-target inhibitor. NDs-IN-1 is mainly used in the study of neurodegenerative diseases.

RIP1 kinase inhibitor 9 (compound SY-1) is a selective RIP kinase inhibitor. RIP1 kinase inhibitor 9 effectively suppresses the central inflammatory response induced by epilepsy. RIP1 kinase inhibitor 9 inhibits Z-VAD-FMK (HY-16658B)-induced necroptosis in HT-29 cells with an EC₅₀ of 7.04 nM.

RIPK2-IN-8 is an orally active and highly selective RIPK2 inhibitor (IC₅₀ = 11 nM). RIPK2-IN-8 is highly selective for RIPK2 over RIPK1 (IC₅₀ > 30,000 nM) and has a moderate inhibitory effect on RIPK3 (IC₅₀ = 44.61 nM). RIPK2-IN-8 inhibits the NOD2-RIPK2 signaling pathway and the expression of the inflammatory cytokines IL-6 and TNFα, thereby exerting anti-inflammatory effects. RIPK2-IN-8 has demonstrated anti-inflammatory and hepatoprotective effects in an acute liver injury (ALI) model and can be used in ALI research.

Fosizensertib is the inhibitor for RIP-1 kinase and can be used in researchs of ulcerative colitis.

RIPK1-IN-33 is a blood-brain barrier-permeable and orally active RIPK1 inhibitor, with an IC₅₀ of 0.115 μM. RIPK1-IN-33 demonstrates remarkable anti-ferroptosis activity, radical scavenging capacity (IC₅₀ = 123.3 μM), and anti-lipid peroxidation effects (IC₅₀ = 9.72 μM). RIPK1-IN-33 markedly reduces cerebral infarction volume and improves neurological function scores in transient middle cerebral artery occlusion (tMCAO) model. RIPK1-IN-33 can be used for the study of ischemic stroke.

RIPK1-IN-41 is an orally active RIPK1 inhibitor with an IC₅₀ of 92 nM and a K_D of 106.8 nM. RIPK1-IN-41 reduces the phosphorylation level of RIPK1, inhibits necrosome formation, blocks the activation of RIPK3 and MLKL, maintains mitochondrial and lysosomal functions, preserves cell membrane integrity, and suppresses necroptosis. RIPK1-IN-41 alleviates hypothermia and multi-organ damage in a mouse model of systemic inflammatory response syndrome induced by mTNF-α. RIPK1-IN-41 is applicable to research related to systemic inflammatory response syndrome.

RIPK3-IN-8 is an orally active and selective RIPK3 inhibitor with a K_d of 150 nM. RIPK3-IN-8 disrupts the formation of the RIPK3-MLKL necrosome and reduces the phosphorylation of downstream MLKL. RIPK3-IN-8 inhibits necroptosis. RIPK3-IN-8 increases the survival rate in a mouse model of TNF-α/Z-VAD-fmk (HY-16658B)-induced systemic inflammatory response syndrome. RIPK3-IN-8 is used for the research of systemic inflammatory response syndrome.

IL-6/RIPK3-IN-1 is an inhibitor of IL-6, RIPK3 and BRD4, with IC₅₀ values of 0.22, 1.32 and 5.91 μM, respectively. IL-6/RIPK3-IN-1 can be used in studies related to inflammation and tissue damage.

RIPK1-IN-40 (Compound 51) is a RIPK1 inhibitor and anti-necroptotic agent (with an EC₅₀ of 0.07 μM against necroptosis). RIPK1-IN-40 binds to the kinase domain of RIPK1, forms hydrogen bond interactions with Met95, and establishes additional polar contacts with Asp156 to stabilize binding, thereby inhibiting necroptosis. RIPK1-IN-40 can be used for the research of colorectal cancer.

RIPK1-IN-42 is an orally active RIPK1 inhibitor with a K_d of 21 nM. RIPK1-IN-42 inhibits the phosphorylation of RIPK1, suppresses the phosphorylation of downstream RIPK3 and MLKL, blocks necrosome formation, and inhibits necroptosis. RIPK1-IN-42 alleviates hypothermia, suppresses the elevation of pro-inflammatory cytokine levels, and reduces organ damage. RIPK1-IN-42 can be used for the research of systemic inflammatory response syndrome.

Necrostatin-21 (Compound Nec-21) is a necroptosis inhibitor with an EC₅₀ of 0.5 μM. Necrostatin-21 has a dual inhibitory effect on the RIP1 and JNK3 kinases. Necrostatin-21 can be used for the researches of infection, cardiovascular and neurological disease, such as Alzheimer disease .

CSLP43 is a selective RIPK2 and XIAP inhibitor with an IC₅₀ of 19.9 nM against human RIPK2. CSLP43 binds to the ATP-binding pocket of RIPK2 and disrupts the interaction between RIPK2 and the BIR2 domain of XIAP or cIAP1. CSLP43 inhibits RIPK2 ubiquitination, NOD1-dependent inflammatory signaling pathways, NOD2-dependent inflammatory signaling pathways, as well as NF-κB activation associated with NOD agonists. CSLP43 is selective for the NOD1/NOD2 signaling pathway and does not inhibit the kinase activity of RIPK1 or RIPK3. CSLP43 is applicable to research related to Crohn's disease, Blau syndrome, early-onset sarcoidosis and early-onset inflammatory bowel disease.

RIPK1-IN-39 (compound 2) is a potent and selective RIPK1 inhibitor (IC₅₀ = 69.40 nM) exhibiting >100-fold selectivity over RIPK3 (IC₅₀ = 6946 nM). RIPK1-IN-39 protects HT-22 and HT-29 cells from necroptosis by inhibiting the phosphorylation and activation of the RIPK1-RIPK3-MLKL pathway. RIPK1-IN-39 demonstrates neuroprotective effects in a rat model of middle cerebral artery occlusion (MCAO). RIPK1-IN-39 can be used for acute ischemic stroke (AIS) research.

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.

AZ'320 is an ATP-competitive necroptosis (EC₅₀ of 4.9 μM) inhibitor and a RIPK1 (pK_D of 5.45) inhibitor. AZ'320 inhibits necroptosis by inhibiting RIPK1 phosphorylation. AZ’320 prevents mortality of the mice and rescues temperature and body weight in SIRS mice models. AZ'320 can be used for researches of cancer and inflammation.

WJH-C19 is an orally active RIPK1 inhibitor with an IC₅₀ of 5.7 nM. WJH-C19 inhibits the RIPK1/RIPK3/MLKL signaling axis, blocks RIPK1 phosphorylation, suppresses the phosphorylation of downstream RIPK3 and MLKL, disrupts necrosome formation, and exhibits protective effects against necroptosis (Apoptosis) in multiple cell lines. WJH-C19 ameliorates symptoms of inflammatory bowel disease in a mouse colitis model by regulating the necroptosis pathway. WJH-C19 alleviates inflammation and bone destruction in a mouse model of rheumatoid arthritis. WJH-C19 is applicable to research related to inflammatory bowel disease and rheumatoid arthritis.

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.

RIPK1-IN-29 (Compound 22) is a RIPK1 inhibitor, with an IC₅₀ of 6.9 nM. RIPK1-IN-29 exerts anti-necroptotic (Apoptosis) activity by inhibiting RIPK1. In a TNF-α-induced in vivo inflammation model, at a dose of 10 mg/kg, RIPK1-IN-29 can protect mice from hypothermia and death. RIPK1-IN-29 can be applied to the research field of inflammatory diseases.