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-14
0 ImagesCat. No.: HY-146758CAS No.: 2919964-79-5RIPK1-IN-14 (Compound 41) is a potent inhibitor of RIPK1 with an IC50 value of 92 nM. RIPK1-IN-14 shows a significant anti-necroptotic effect in a necroptosis model in U937 cells.
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SZM-1209
0 ImagesCat. No.: HY-149052CAS No.: 2919801-86-6SZM-1209 is an orally active, potent and specific RIPK1 inhibitor, with a Kd of 85 nM. SZM-1209 exhibits high anti-necroptotic activity (EC50=22.4 ± 8.1 nM). SZM-1209 shows anti-SIRS (systemic inflammatory response syndrome), and anti-ALI (acute lung injury) effects.
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RIPK1 ligand-Linker Conjugate-2
0 ImagesCat. No.: HY-189353RIPK1 ligand-Linker Conjugate-2 is a conjugate of a RIPK1 ligand and a linker, in which the RIPK1 ligand is RIPK1-IN-37 (HY-179235) and the linker is Boc-2,6-Diazaspiro[3.3]heptane-Py-Ph-acid (HY-189354). RIPK1 ligand-Linker Conjugate-2 can be used to synthesize RIPK1 PROTAC degraders, such as LD5095 (HY-189352).
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RIPK1-IN-22
0 ImagesCat. No.: HY-162237RIPK1-IN-13 (compound 28) is a selective inhibitor for receptor-interacting serine/threonine-protein kinase 1 (RIPK1), the inhibitory activity is measured by ADP-Glo Kinase Assay with a pKi of 7.66. RIPK1-IN-13 inhibits human leukaemia cells U937 with a pIC50 of 7.2.
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RIPK1-IN-36
0 ImagesCat. No.: HY-179323CAS No.: 2924736-22-9RIPK1-IN-36 (Example 4.1) is a RIPK1 inhibitor with an EC50 of <25 nM. RIPK1-IN-36 can be used for the study of RIPK1-related diseases.
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RIPK1-IN-31
0 ImagesCat. No.: HY-173574CAS No.: 2857845-45-3RIPK1-IN-31 (Compound 36) is a selective allosteric modulator of RIPK1 (receptor-interacting protein kinase 1) with an IC50 value of 16 nM. RIPK1-IN-31 is promising for research of infectious, autoimmune, and neurodegenerative diseases.
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NDs-IN-1
0 ImagesCat. No.: HY-158334CAS No.: 3033806-97-9(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.
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RIPK1-IN-41
0 ImagesCat. No.: HY-183781RIPK1-IN-41 is an orally active RIPK1 inhibitor with an IC50 of 92 nM and a KD 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.
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RIPK1-IN-40
0 ImagesCat. No.: HY-181944RIPK1-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.
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RIPK1-IN-42
0 ImagesCat. No.: HY-184686RIPK1-IN-42 is an orally active RIPK1 inhibitor with a Kd 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.
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Necrostatin-21
0 ImagesCat. No.: HY-W319332CAS No.: 169136-33-8Necrostatin-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 .
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Akt RIMTAC-1
0 ImagesCat. No.: HY-187500Akt RIMTAC-1 is a Akt RIMTAC degrader (a PROTAC-like agent) with a DC50 of 3.52 μM. Akt RIMTAC-1 forms a ternary complex with AKT and RIPK1, and recruits the VHL E3 ligase complex to mediate ubiquitination and proteasomal degradation. Akt RIMTAC-1 does not alter AKT1 mRNA levels (pink: AKT ligand-5 (HY-187501); blue: RIPK1-ligand-4 (HY-187391); black: Linker (HY-23166)).
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RIPK1-IN-39
0 ImagesCat. No.: HY-180806CAS No.: 3065634-42-3RIPK1-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.
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WJH-C19
0 ImagesCat. No.: HY-181596Purity: 98.65%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.
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RIPK1-IN-29
0 ImagesCat. No.: HY-170232RIPK1-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.
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RIPK1-IN-23
0 ImagesCat. No.: HY-157963CAS No.: 3031534-16-1RIPK1-IN-23 (compound 19) is a RIPK1 inhibitor with potent anti-necroptotic effects in HT-29 cells (EC50 of 1.7 nM). RIPK1-IN-23 shows anti-inflammatory activities.
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Nec-3a
0 ImagesCat. No.: HY-18899CAS No.: 1504558-72-8Nec-3a is a Necrostatin-3 analogue. Nec-3a is a RIP1 inhibitor (IC50: 0.44 μM). Nec-3a inhibits the autophosphorylation activity of the RIP1 kinase domain.
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RIP1 kinase inhibitor 4
0 ImagesCat. No.: HY-153434CAS No.: 2919836-00-1RIP1 kinase inhibitor 4 (Example 3) is a BBB-penetrable RIP1 kinase inhibitor (EC50: <100 nM). RIP1 kinase inhibitor 4 can be used for the research of cell programming necrosis-related diseases. RIP1 kinase inhibitor 4 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
