Role of Receptor Interacting Protein (RIP) kinases in cancer

Ermine, Kaylee; Yu, Jian; Zhang, Lin

doi:10.1016/j.gendis.2021.10.007

Cited by 19 publications

(13 citation statements)

References 162 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous lines of evidence have suggested that the RIP1 kinase is subject to genetic, epigenetic and expression changes in tumor cells, and necroptosis has been closely related to the occurrence, development, metastasis, and drug resistance mechanisms of tumor cells. ,, Depending on the tumor type and cell environment, RIP1 can exert a tumor promoting or a tumor suppressing effect. The RIP1 level is elevated in glioblastoma, melanoma, lung cancer, pancreatic ductal adenocarcinoma (PDAC), gastric cancer, gallbladder cancer, and other diseases. − This increase in RIP1 leads to NF-κB activation and enhanced cell proliferation.…”

Section: Rip1 Structure and Biological Functions: Implications For Hu...mentioning

confidence: 99%

“…Recently, the development of RIP1 inhibitors has been focused on optimizing the inhibitor kinase selection specificity, effectiveness, and pharmacokinetic (PK) properties. As RIP1 is a newly discovered and potential multifaceted-disease-related drug target, ,,,− many new RIP1 kinase inhibitors with high selectivity have been reported, and some of these inhibitors have been entered into clinical trials, such as a phase I clinical trial for ALS and phase II clinical trials for psoriasis, RA, and ulcerative colitis (UC). , Based on the current understanding of RIP1 regulatory mechanisms and recent evidence indicating pathological roles for RIP1 in human diseases, we highly anticipate that our review of the recent developments of small-molecule inhibitors targeting the RIP1 kinase and perspectives on related drug development strategies will contribute to future research into the kinase inhibitor field.…”

Section: Introductionmentioning

confidence: 99%

“…The specificity of RIP1-mediated TNFR1 signal transduction prevents unwanted TNF responses in the central nervous system (CNS). ,, Highly selective small-molecule RIP1 inhibitors can penetrate the blood–brain barrier (BBB), indicating that these inhibitors are feasible targeted therapies for neuroinflammation and cell death. RIP1 has become a potential therapeutic target for the treatment of many human chronic neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), and Parkinson’s disease (PD), as well as acute neurological diseases, such as cerebral ischemia, stroke, and traumatic brain injury. , At the intersection of cell death pathways and host-defense pathways, RIP1 may be leveraged for new therapeutic opportunities for immune and autoinflammatory diseases, such as inflammatory bowel disease (IBD), psoriasis, sepsis, rheumatoid arthritis (RA), and multiple sclerosis (MS), and cancers, including glioblastoma, melanoma, lung cancer, pancreatic cancer (PCa), gastric cancer, and gallbladder cancer …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Small-Molecule Receptor-Interacting Protein 1 (RIP1) Inhibitors as Therapeutic Agents for Multifaceted Diseases: Current Medicinal Chemistry Insights and Emerging Opportunities

et al. 2022

View full text Add to dashboard Cite

As a serine/threonine protein kinase, receptor-interacting protein 1 (RIP1) plays an important role in regulating the pathways in programmed cell death. Multifaceted human diseases (e.g., autoimmune diseases, inflammatory diseases, neurodegenerative diseases, and tumors) are closely related to RIP1 kinase. Therefore, small-molecule RIP1 inhibitors with precise targeting and good penetrability have recently been used in potentially therapeutic methods, attracting extensive researcher interest. GSK2982772, developed by GlaxoSmithKline (GSK), became the world’s first RIP1 inhibitor approved for clinical research in 2014. Nine clinical trials assessing GSK2982772 have been performed. The most recent direction in RIP1 inhibitor development has been focused on RIP1 small-molecule inhibitors with higher potency, selectivity, and metabolic stability. In this Perspective, considering the structure, biological functions, and disease relevance of RIP1, we summarize the recent research progress in RIP1 small-molecule inhibitor development based on different binding modalities and discuss prospective strategies for designing additional RIP1 therapeutic agents.

show abstract

Section: Rip1 Structure and Biological Functions: Implications For Hu...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Small-Molecule Receptor-Interacting Protein 1 (RIP1) Inhibitors as Therapeutic Agents for Multifaceted Diseases: Current Medicinal Chemistry Insights and Emerging Opportunities

et al. 2022

View full text Add to dashboard Cite

show abstract

“…16,18 Expectedly, RIP1 is constitutively ubiquitinated in various cancer cells and thus promotes cancer cell survival. 19 AEG407730, an IAP antagonist designed to bind with the BIR3 domain of cIAP1/2 with nanomolar affinity, can sensitize cancer cells for caspase-8-dependent apoptosis via autoubiquitination-mediated proteasomal degradation of cIAP1/2 and activation of TNF-α autocrine signaling. 17 Also, various other means like suppression of cIAP1 expression, its sequestration with SMAC mimetics, and promotion of its degradation by PROTAC technology are being explored to control the cIAP1 level in cancer cells.…”

Section: ■ Introductionmentioning

confidence: 99%

Stable RNA G-Quadruplex in the 5′-UTR of Human cIAP1 mRNA Promotes Translation in an IRES-Independent Manner

Singha Roy,

Majumder,

Saha

2024

Biochemistry

View full text Add to dashboard Cite

RNA G-quadruplex (rG4) structures can influence the fate and functions of mRNAs, especially the translation process. The presence of rG4 structures in 5′-untranslated regions (5′-UTRs) of mRNAs generally represses translation. However, rG4 structures can also promote internal ribosome entry site (IRES)-mediated translation as one of its determinants. Here, we report the identification of an evolutionary conserved rG4-forming sequence motif at the extreme 5′-end of the unusually long 5′-UTR (1.7 kb) in the transcript of human cIAP1 gene encoding the cellular inhibitor of apoptosis protein-1 that promotes cell survival by suppressing apoptosis and is overexpressed in various cancer cells. Expectedly, NMR study, CD spectroscopy, and UV melting assay confirm the formation of a potassium ion-dependent intramolecular and parallel rG4 structure at the sequence stretch. Moreover, the G4-RNA-specific precipitation using biotin-linked biomimetic BioCyTASQ validates the formation of the rG4 structure in the cIAP1 5′-UTR in cells. Interestingly, disruption of the rG4 structure in the cIAP1 5′-UTR results in a dramatic reduction in translation of the downstream luciferase reporter in cells, suggesting a translation-promoting effect of the rG4 structure, contrary to many earlier reports. Furthermore, enhancement of translation by the cIAP1 rG4 structure occurs in an IRES-independent manner.

show abstract

“…This review aims to summarize the recent progress in the designs and characterizations of RIPK2 inhibitors and degraders from a medicinal chemistry perspective. Details of the NODs/RIPK2 cellular signaling as well as their roles in inflammatory diseases can be found in recently published reviews ( Chen et al, 2009 ; Jun et al, 2013 ; Caruso et al, 2014 ; Irving et al, 2014 ; Humphries et al, 2015 ; Ermine et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Recent advances in the development of RIPK2 modulators for the treatment of inflammatory diseases

2023

View full text Add to dashboard Cite

Receptor-interacting serine/threonine kinase 2 (RIPK2) is a vital immunomodulator that plays critical roles in nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and Toll-like receptors (TLRs) signaling. Stimulated NOD1 and NOD2 interact with RIPK2 and lead to the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPK), followed by the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-12/23. Defects in NOD/RIPK2 signaling are associated with numerous inflammatory diseases, including asthma, sarcoidosis, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), multiple sclerosis, and Blau syndrome. As RIPK2 is a crucial element of innate immunity, small molecules regulating RIPK2 functions are attractive to establish novel immunotherapies. The increased interest in developing RIPK2 inhibitors has led to the clinical investigations of novel drug candidates. In this review, we attempt to summarize recent advances in the development of RIPK2 inhibitors and degraders.

show abstract

Role of Receptor Interacting Protein (RIP) kinases in cancer

Cited by 19 publications

References 162 publications

Small-Molecule Receptor-Interacting Protein 1 (RIP1) Inhibitors as Therapeutic Agents for Multifaceted Diseases: Current Medicinal Chemistry Insights and Emerging Opportunities

Small-Molecule Receptor-Interacting Protein 1 (RIP1) Inhibitors as Therapeutic Agents for Multifaceted Diseases: Current Medicinal Chemistry Insights and Emerging Opportunities

Stable RNA G-Quadruplex in the 5′-UTR of Human cIAP1 mRNA Promotes Translation in an IRES-Independent Manner

Recent advances in the development of RIPK2 modulators for the treatment of inflammatory diseases

Contact Info

Product

Resources

About