RIPK1
RIPK1 is a stress-sensing serine/threonine kinase that coordinates cell survival, inflammatory signaling, apoptosis, and immunogenic cell death[1]. Mechanistically, RIPK1 acts within TNF-related signaling complexes, where its scaffold function restrains caspase-8- and RIPK3-dependent lethality while its kinase activity promotes regulated cell death under defined stimuli[2]. In necroptosis, RIPK1 cooperates with RIPK3 to assemble a phosphorylation-dependent complex, and RIPK3 phosphorylates MLKL to drive membrane-disruptive necrotic death[3][4]. Compared with related RIPK3 and MLKL, RIPK1 is distinguished by separable kinase-dependent death signaling and kinase-independent scaffold protection, making isoform-specific interpretation essential in experimental design[5][6]. Disease models link RIPK1 activity to ALS axonal degeneration, Alzheimer’s disease microglial responses, and human immunodeficiency or intestinal inflammation caused by RIPK1 loss of function[7][8][9]. For experimental applications, necrostatins and clinical RIPK1 inhibitors provide tools to test kinase-dependent biology, but inhibitor selectivity and scaffold-preserving effects require careful controls[10][11].
References:
- [1]. Clucas J, et al. Roles of RIPK1 as a stress sentinel coordinating cell survival and immunogenic cell death. Nat Rev Mol Cell Biol. 2023 Nov;24(11):835-852. [Content Brief]
- [2]. Dillon CP, et al. RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3. Cell. 2014 May 22;157(5):1189-202. [Content Brief]
- [3]. Cho YS, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009 Jun 12;137(6):1112-23. [Content Brief]
- [4]. Wang H, et al. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell. 2014 Apr 10;54(1):133-146. [Content Brief]
- [5]. Polykratis A, et al. Cutting edge: RIPK1 Kinase inactive mice are viable and protected from TNF-induced necroptosis in vivo. J Immunol. 2014 Aug 15;193(4):1539-1543. [Content Brief]
- [6]. Dannappel M, et al. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature. 2014 Sep 4;513(7516):90-4. [Content Brief]
- [7]. Ito Y, et al. RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS. Science. 2016 Aug 5;353(6299):603-8. [Content Brief]
- [8]. Ofengeim D, et al. RIPK1 mediates a disease-associated microglial response in Alzheimer's disease. Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8788-E8797. [Content Brief]
- [9]. Li Y, et al. Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):970-975. [Content Brief]
- [10]. Degterev A, et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol. 2008 May;4(5):313-21. [Content Brief]
- [11]. Harris PA, et al. Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases. J Med Chem. 2017 Feb 23;60(4):1247-1261. [Content Brief]
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RIPK1 Related Products (67)
Related Products (67)
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Antibodies (1)
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RIPK1-IN-19
0 ImagesRIPK1-IN-19 is a selective RIPK1 inhibitor (IC50=15 nM). RIPK1-IN-19 does not show obvious activity against RIPK2, RIPK3, and RIPK4. RIPK1-IN-19 displays potent protective activity in TNFα-induced systemic inflammatory response syndrome (SIRS) model and Imiquimod (IMQ)-induced psoriasis model. RIPK1-IN-19 can be used in research on inflammation and immune system diseases.
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KBU2046
0 ImagesKBU2046 is an orally active transforming growth factor-β (TGF-β1) inhibitor. KBU2046 reduces integrin family protein expression, decreases Raf, RIPK1 and ERK phosphorylation to deactivate the ERK signaling pathway, and down-regulates genes linked to TGF-β1 maturation. KBU2046 suppresses tumor cell motility, impedes cancer invasion and metastasis, and inhibits human ESCC growth and metastasis in a murine model. KBU2046 can be used for the researches of triple-negative breast cancer and esophageal squamous cell carcinoma.
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SZM679
0 ImagesSZM679 is a potent, orally active and selective RIPK1 inhibitor with Kd values of 8.6 nM and >5000 nM for RIPK1 and RIPK3, respectively. SZM679 reverses the tumor necrosis factor-induced systemic inflammatory response. SZM679 decreases the Tau hyperphosphorylation, neuroinflammation, and the RIPK1 phosphorylation level in the hippocampus and cortex. SZM679 can be used in research of Alzheimer's disease (AD).
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NecroIr2
0 ImagesCat. No.: HY-148366Purity: 98.02%NecroIr2 is an iridium(III) complex, serves as necroptosis inducers in Cisplatin (HY-17394)-resistant lung cancer cells (A549R). NecroIr2 selectively accumulates in mitochondria, leading to oxidative stress and loss of mitochondrial membrane potential (MMP). NecroIr2 activates receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like pseudokinase (MLKL), and regulates CDK4 expression.
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NecroIr1
0 ImagesCat. No.: HY-148365Purity: 98.53%NecroIr1 is an iridium(III) complex, serves as necroptosis inducers in Cisplatin (HY-17394)-resistant lung cancer cells (A549R). NecroIr1 selectively accumulates in mitochondria, leading to oxidative stress and loss of mitochondrial membrane potential (MMP). NecroIr1 activates receptor-interacting serine-threonine kinase 3 (RIPK3) and Mixed Lineage Kinase (MLKL), and regulates CDK4 expression.
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RIP1-IN-1
0 ImagesCat. No.: HY-173185RIP1-IN-1 is an orally active RIP1 inhibitor with strong RIP1 binding affinity (Kd: 110 nM). RIP1-IN-1 exhibits strong anti-necroptosis activity. RIP1-IN-1 effectively inhibits the formation of necrosomes by blocking the phosphorylation of RIP1, RIP3 and MLKL signaling pathways. RIP1-IN-1 inhibits necroptosis and can be used in the study of acute liver injury.
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Zharp1-163
0 ImagesCat. No.: HY-178163Zharp1-163 is a dual inhibitor of ferroptosis and necroptosis. Zharp1-163 effectively blocks ferroptosis by reducing reactive oxygen species (ROS) levels and inhibits necroptosis by potently and selectively targeting RIPK1 kinase activity (KD = 240 nM; IC50 = 406.1 nM). Zharp1-163 inhibits the cellular activation of RIPK1, RIPK3 and MLKL in response to necroptotic stimulation. Zharp1-163 markedly attenuates TNF-α (HY-P1875)-induced systemic inflammatory syndrome, including the prevention of TNF-α-induced mortality and hypothermia in mice. Zharp1-163 significantly alleviates acute kidney injury associated with both necroptosis and ferroptosis in models induced by Cisplatin (HY-17394) and ischemia-reperfusion. Zharp1-163 can be used for the study of diseases associated with cell death pathways, such as kidney disease.
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RIPK1-IN-34
0 ImagesCat. No.: HY-178464CAS No.: 3065634-19-4RIPK1-IN-34 is a selective, brain-penetrant RIPK1 inhibitor (IC50 = 126.70 nM) with almost no inhibitory effect on RIPK3 (IC50 ＞ 10, 000 nM). RIPK1-IN-34 offers substantial neuroprotection by inhibiting the phosphorylation of RIPK1, RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) within the necroptosis pathway. RIPK1-IN-34 shows the neuroprotective effect in a rat middle cerebral artery occlusion (MCAO) model. RIPK1-IN-34 can be used for the study of anti-acute ischemic stroke (AIS).
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Tat-ASIC1a (1-20) (mouse, rat)
0 ImagesCat. No.: HY-P10977Tat-ASIC1a (1-20) (mouse, rat) is a competitive ASIC1a membrane-penetrating peptide. Tat-ASIC1a (1-20) (mouse, rat) has significantly neuroprotection effects, and reduces neuronal damage against acidotoxicity by targeting the ASIC1a-RIPK1 pathway and auto-inhibitory mechanism. Tat-ASIC1a (1-20) (mouse, rat) effectively protects brains from ischemic injury in ischemic stroke mice model. Tat-ASIC1a (1-20) (mouse, rat) can be used for neurodegenerative diseases research, such as Huntington disease and Parkinson’s disease.
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RIPK1-IN-18
0 ImagesCat. No.: HY-160216CAS No.: 2682889-01-4RIPK1-IN-18 (compound i) is a potent inhibitor of RIPK1. RIPK1-IN-18 can be used in autoimmune diseases research.
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VWK147
0 ImagesCat. No.: HY-181062VWK147 is a second-generation HSP90 C-terminal domain (CTD) inhibitor. VWK147 targets the CTD dimerization interface, prevents HSP90 CTD dimerization, disrupts co-chaperone PPID binding to HSP90 CTD, and inhibits HSP90 chaperone function dependent on dimerization. VWK147 reduces protein levels of HSP90 client proteins ULK1, RIPK1, and CDK4 without inducing a heat shock response. VWK147 induces cell death, including apoptosis, in Cisplatin (HY-17394)-sensitive and -resistant urothelial carcinoma cells. VWK147 induces LC3-II accumulation, inhibits autophagosome-lysosome fusion to block canonical autophagy, and induces non-canonical LC3 lipidation independent of ULK1 and PIK3C3 complexes. VWK147 can be used for the research of urothelial carcinoma.
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RIPK1-IN-43
0 ImagesCat. No.: HY-187460RIPK1-IN-43 is a triazolopyridine compound and also a RIPK1 inhibitor. RIPK1-IN-43 can be used in the research of diseases associated with abnormal RIPK1, such as multiple sclerosis, Parkinson's disease, non-alcoholic steatohepatitis, etc.
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RIPK1-IN-38
0 ImagesCat. No.: HY-179680CAS No.: 3092834-30-2RIPK1-IN-38 is an orally active RIPK1 inhibitor with an IC50 value of 27 nM. RIPK1-IN-38 can inhibit the phosphorylation of RIPK1 and its downstream signaling molecules RIPK3 and MLKL. RIPK1-IN-38 exhibits anti-necroptotic activity. RIPK1-IN-38 has excellent anti-inflammatory efficacy in both the SIRS model and GVHD model. RIPK1-IN-38 can be used for the research of inflammatory and immune-related diseases.
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RIPK1-IN-11
0 ImagesCat. No.: HY-144276CAS No.: 2173557-02-1RIPK1-IN-11 is a potent and orally active RIPK1 inhibitor (Kd=9.2 nM; IC50=67 nM). RIPK1-IN-11 inhibits necroptosis in both human and mouse cells (EC50=17-30 nM). Anti-inflammatory activity.
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PB830
0 ImagesCat. No.: HY-153437CAS No.: 2428401-23-2PB830 (compound 41) is a potent receptor interacting protein 1 kinase (RIP1) Inhibitor with an IC50 of <100 nM for human RIP1. PB830 has an EC50 of 1-100 nM in the cell necrosis assay.
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LT-1339-553
0 ImagesCat. No.: HY-184001CAS No.: 3078683-57-2LT-1339-553 is a selective, orally active RIPK1 inhibitor with IC50 values of 4.32, 95.74 and 84.33 nM against RIPK1, RIPK2 and RIPK3, respectively. LT-1339-553 exerts anti-necroptotic activity by inhibiting the AKT/PI3K/NF-κB pathway and the IL-17 pathway. LT-1339-553 reduces liver injury, inflammatory responses and collagen deposition. LT-1339-553 can be used in studies related to schistosomiasis-induced liver fibrosis.
