RIPK1 Peptide
- Known as:
- RIPK1 Peptide
- Catalog number:
- 5389P
- Product Quantity:
- 0.05 mg
- Category:
- -
- Supplier:
- Prosci
- Gene target:
- RIPK1 Peptide
Related genes to: RIPK1 Peptide
- Gene:
- RIPK1 NIH gene
- Name:
- receptor interacting serine/threonine kinase 1
- Previous symbol:
- -
- Synonyms:
- RIP
- Chromosome:
- 6p25.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-05-07
- Date modifiied:
- 2015-11-17
Related products to: RIPK1 Peptide
Related articles to: RIPK1 Peptide
- Necroptosis is a lytic form of programmed cell death that requires activation of the RIPK1/3-MLKL complex and results in plasma membrane permeabilization. Although the protein components governing necroptosis are well defined, the lipid determinants of this process remain poorly understood. Here, we combined lipidomics, pharmacological perturbations of sphingolipid metabolism and functional assays to identify sphingolipid pathways that contribute to necroptotic cell death. Using a panel of small molecule inhibitors, we found that inhibition of acid sphingomyelinase (ASMase) with ARC39 restored cell viability and membrane integrity during necroptosis without altering canonical necroptotic signaling. Lipidomic analysis revealed that ARC39 treatment prevented ceramide accumulation in necroptosis, linking reduced ceramide levels to decreased membrane permeability. Interestingly, ARC39 treatment did not reduce total cellular levels of phosphorylated MLKL (pMLKL) nor its membrane association, suggesting that the observed decrease in membrane permeability arises downstream of MLKL activation. Instead, our findings support a model in which the reduction of ceramide levels impairs productive membrane interactions by pMLKL. Consistent with this interpretation, genetic knockdown of ASMase similarly resulted in increased cell viability, decreased membrane permeabilization, and decreased ceramide levels during necroptosis, further linking ceramide homeostasis to necroptotic membrane damage. Together, these results indicate that ASMase-derived ceramides are important for efficient MLKL-mediated membrane permeabilization in necroptosis. - Source: PubMed
Publication date: 2026/07/02
Pilapil Luis Agustin EChitkara ShwetaAtilla-Gokcumen G Ekin - Depression, a prevalent mental health disorder, has attracted increasing attention owing to its association with neuroinflammation. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) plays a crucial role in maintaining cellular and tissue homeostasis by regulating inflammatory responses and cell death signalling pathways, both of which are closely linked to various physiological and pathological processes. Accordingly, RIPK1 functions as an upstream kinase that modulates inflammation and cell death. Tumour necrosis factor-α (TNF-α), a key pro-inflammatory cytokine implicated in the pathogenesis of various human diseases, acts as a principal upstream activator of RIPK1. Accumulating evidence further indicates that RIPK1 may contribute to a detrimental neuroinflammatory environment in mental disorders such as depression. However, its specific regulatory role and underlying mechanisms in depression remain incompletely understood. This review first summarises current advances in understanding the molecular structure and biological functions of RIPK1, with particular emphasis on multiple cellular pathways associated with depression. Subsequently, it discusses the mechanisms by which RIPK1 participates in the pathological process of depression, including its role in neuroinflammation and synaptic plasticity. Finally, we outline the effects of RIPK1 inhibitors in animal models, which have been shown to prevent neuronal cell death and reduce neuroinflammation. Collectively, these findings suggest that targeting RIPK1 may represent a promising therapeutic strategy with potential for clinical translation, highlighting its value as a potential therapeutic target in depression. However, further work is still needed to bridge the gap between preclinical mechanisms related to the RIPK1 inflammatory pathway and their actual clinical efficacy. - Source: PubMed
Publication date: 2026/07/10
Chen Xiao-QunZhuang Yu-ChiGuan Wei - Necrostatin-1 (Nec-1), a widely used RIPK1 inhibitor and necroptosis probe, also suppresses ferroptosis, complicating distinction between these cell death pathways. Here, we show that the thiohydantoin moiety of Nec-1 reacts with hydroperoxides to form a sulfenic acid intermediate capable of trapping peroxyl radicals and inhibiting the lipid peroxidation (LPO) that drives ferroptosis. To investigate this mechanism, several analogs were synthesized and evaluated in the FENIX cell-free LPO assay. Anti-LPO activity was enhanced by increasing steric bulk or nucleophilicity around the thiocarbonyl, relocating the thiohydantoin methyl group, or introducing a fully conjugated linker between the thiohydantoin and indole rings. The fully conjugated analog of Nec-1 (dsaturated Nec-1 or dsNec-1) was isolated as a stable species from preparative reactions of Nec-1 and a hydroperoxide, suggesting it mediates Nec-1's antiferroptotic effects. Desaturated derivatives were, however, inactive against necroptosis, indicating that the Nec-1 scaffold is unsuitable for dual-pathway inhibitor development. - Source: PubMed
Publication date: 2026/07/10
Al-Farhan AmrNayal Onkar SPratt Derek A - PANoptosis is a distinct inflammatory and lytic cell death pathway, orchestrated by the PANoptosome and executed through caspases and receptor-interacting protein kinases (RIPKs). Unlike other forms of programmed cell death, PANoptosis integrates components from multiple death signaling cascades. To date, several PANoptosome complexes - such as those nucleated by ZBP1, AIM2, RIPK1, and NLRP12 - have been characterized. These supramolecular assemblies form via domain-domain interactions upon detection of pathogen-associated or damage-associated signals. By eliminating infected and compromised cells, this coordinated pathway helps maintain tissue homeostasis, while its synchronized release of inflammatory cytokines and damage-associated molecular patterns (DAMPs) enhances innate immune responses, resulting in more effective pathogen clearance compared to any single cell death mechanism. Growing evidence underscores the relevance of PANoptosis across a spectrum of pathological conditions, including neurological disorders, infections, inflammatory diseases, cancer, and homeostatic imbalances, often mediated by PANoptosis-associated proteins. In neurological contexts - such as stroke, Parkinson's disease, Alzheimer's disease, and traumatic brain injury - PANoptosis activation correlates with disease progression and prognosis, highlighting its potential as a therapeutic target. In this review, we systematically outline the molecular foundations of PANoptosis, examine its role in neurological diseases, and summarize current pharmacological and methodological strategies for its modulation. A deeper understanding of PANoptosis may inform the identification of novel therapeutic targets for neurological disorders. - Source: PubMed
Publication date: 2026/07/10
Tang QiongyanXu MinminXiao XuemeiCao JingYang Weimin - Acute liver injury (ALI) is characterized by massive hepatocyte necrosis and rapid deterioration of liver function, which is closely associated with a cytokine storm mediated by the excessive activation of macrophages. Currently, there is a lack of effective targeted drugs in clinical practice. This study aimed to investigate the protective effects and mechanisms of protocatechualdehyde (PCA) against ALI. PCA exerts its biological effects by inhibiting macrophage-driven inflammation. The protective effects and mechanisms of PCA were experimentally validated using both in vivo and in vitro assays. In vivo, mice with ALI induced by lipopolysaccharide (LPS), acetaminophen (APAP), or carbon tetrachloride (CCl₄) showed reduced liver tissue damage, decreased serum transaminase levels, and downregulated inflammatory cytokine levels after PCA treatment, indicating that PCA protects against ALI induced by multiple causes. In vitro experiments further demonstrated that, within a safe concentration range, PCA significantly inhibit the expression of inflammatory cytokines in LPS-induced RAW264.7 cells and suppress necroptosis. Mechanistically, PCA functions through multiple pathways. It directly binds to RIPK1 to inhibit necroptosis in macrophages. Furthermore, it downregulates IFN-γ, subsequently blocking the JAK1/STAT1 signaling pathway and reducing the release of IL-17a and Ccl20. A reduction in these cytokines diminishes the infiltration of neutrophils and T cells, thereby improving the inflammatory milieu in ALI. In conclusion, PCA synergistically attenuates macrophage-driven inflammatory injury by inhibiting RIPK1-mediated necroptosis and regulating the IFN-γ/JAK1/STAT1 signaling axis, providing experimental evidence of its potential as a therapeutic agent for ALI. - Source: PubMed
Publication date: 2026/07/09
Hu ChuchuMiao YijiaYan WenjingJia MengyiZhang XiaoyaLi MengjuanSun XiaolongLiu ZiyiLi JunLi HaidiYang Yaru