ADAR1: A Potential Target in Tumor Immunity
ADAR1: A Potential Target in Tumor Immunity
ADAR1 is an important RNA-editing enzyme that catalyzes adenosine-to-inosine (A-to-I) editing in double-stranded RNA (dsRNA), reducing the recognition of endogenous dsRNA by nucleic acid-sensing systems such as MDA5, PKR, and ZBP1. Tumor cells can exploit ADAR1 to maintain RNA immune tolerance, whereas ADAR1 inhibition can reactivate innate immune and cell-death signaling, making it a potential target for cancer immunotherapy.
Keywords: ADAR1; A-to-I RNA editing; double-stranded RNA; MDA5; PKR; ZBP1; viral mimicry; tumor immunity; immune checkpoint blockade
1 Molecular Basis of ADAR1
1.1 The ADAR Family and ADAR1 Isoforms
(1) The ADAR Family
The mammalian ADAR family mainly comprises ADAR1, ADAR2, and ADAR3. ADAR1 and ADAR2 possess A-to-I RNA-editing activity, whereas ADAR3 is mainly expressed in the central nervous system and can bind RNA but is generally considered to lack effective catalytic editing activity. ADAR1 participates extensively in endogenous dsRNA editing and innate immune homeostasis and is currently the most intensively studied ADAR family member in tumor immunity.
(2) ADAR1p110
ADAR1p110 is mainly driven by a constitutive promoter and is predominantly localized in the nucleus. It contains a Zβ domain, three dsRNA-binding domains (dsRBDs), and a C-terminal deaminase domain and primarily participates in nuclear RNA editing and regulation of RNA homeostasis.
(3) ADAR1p150
ADAR1p150 has a longer N-terminus and can be induced by type I and type II interferons. It plays an important role in cytoplasmic RNA homeostasis and innate immune regulation. Compared with p110, p150 additionally contains a Zα domain and nuclear export-related sequences, allowing it to shuttle between the nucleus and cytoplasm. Zα recognizes left-handed helical Z-RNA/Z-DNA and provides the structural basis through which p150 regulates immune recognition of Z-conformation nucleic acids.
Table 1. Major Differences Between ADAR1p110 and ADAR1p150
Feature | ADAR1p110 | ADAR1p150 |
Expression pattern | Constitutive expression | Interferon-inducible with basal expression |
Major localization | Predominantly nuclear | Predominantly cytoplasmic, with nucleocytoplasmic shuttling |
Zα domain | Absent | Present |
Zβ domain | Present | Present |
dsRNA-binding domains | Three | Three |
Deaminase domain | Present | Present |
Major research focus | Nuclear RNA editing and RNA homeostasis | Cytoplasmic dsRNA tolerance, Z-RNA recognition, and innate immune regulation |
1.2 ADAR1 Domains and RNA Recognition
(1) dsRNA-Binding Domains
ADAR1 contains three dsRBDs that bind RNA with double-stranded characteristics and participate in substrate positioning. Substrate selection is influenced not only by nucleotide sequence but also by duplex length, local mismatches, bulges, and secondary structure.
(2) Deaminase Domain
The C-terminal deaminase domain mediates A-to-I catalysis. After binding RNA, ADAR1 positions the target adenosine within the catalytic center and converts it into inosine through hydrolytic deamination. This domain is also an important design region for direct catalytic inhibitors of ADAR1.
(3) Zα Domain
The Zα domain is unique to ADAR1p150 and recognizes nucleic acids in the left-handed Z conformation. This domain allows p150 to participate in Z-RNA-related immune regulatory networks and provides a potential isoform-selective drug-binding site for distinguishing p150 from p110.
(4) Dimerization and Regulation of Editing
ADAR1 can form dimers, and editing efficiency is jointly influenced by protein interactions, RNA binding, and local RNA structure. The actual function of ADAR1 is determined by its protein isoform, substrate structure, cellular localization, and catalytic state and cannot be inferred solely from total protein expression.
1.3 Mechanism of A-to-I RNA Editing
(1) Conversion of A to I
ADAR1 catalyzes the hydrolytic deamination of adenosine (A) to inosine (I). Inosine behaves primarily like guanosine during base pairing and can pair with cytosine. A-to-I editing is therefore generally detected as an A-to-G change in RNA sequencing.
(2) Editing in Coding Regions
When editing occurs within a protein-coding region, it may alter the codon and the resulting protein product. AZIN1 is a representative tumor-associated editing substrate, and site-specific editing of AZIN1 has been associated with cellular proliferation and malignant phenotypes in certain tumors.
(3) Editing in Noncoding Regions
A large proportion of A-to-I editing in humans occurs within repeat-derived noncoding regions. Rather than altering protein sequences, this type of editing changes local dsRNA base pairing and structural features, reducing the probability of recognition by innate immune-sensing systems.
1.4 Major Sources of Immunogenic dsRNA
(1) IR-Alu
The human genome contains numerous Alu repetitive elements. Oppositely oriented Alu sequences within the same transcript can undergo complementary base pairing to form inverted-repeat Alu structures (IR-Alu). Double-stranded regions generated by IR-Alu are major sources of endogenous dsRNA and A-to-I editing in human cells.
(2) Endogenous Repetitive Elements
Endogenous retroelements and other repetitive sequences can also generate transcripts with double-stranded characteristics. Relief of DNA methylation and repressive chromatin states increases the abundance of these transcripts and can further elevate the intracellular dsRNA burden.
(3) Natural Antisense Transcripts
Certain cis-natural antisense transcripts (cis-NATs) can form complementary double-stranded regions with their corresponding RNAs and thereby enter ADAR1-mediated editing and innate immune-sensing networks.
2 How ADAR1 Maintains RNA Immune Homeostasis
2.1 MDA5–MAVS–Type I Interferon Signaling
(1) MDA5 Recognition of dsRNA
MDA5 primarily recognizes long cytoplasmic dsRNA. ADAR1-mediated editing alters the continuous double-stranded characteristics and immunogenicity of endogenous dsRNA, reducing the probability that MDA5 will recognize self-RNA as an abnormal nucleic acid.
(2) MAVS and IFN Production
Following activation, MDA5 transmits signals through mitochondrial antiviral-signaling protein MAVS, which activates TBK1 and IRF3/IRF7 and promotes the expression of IFNB1 and a series of antiviral and inflammation-related genes.
(3) Self-RNA Tolerance
When ADAR1 editing is defective, insufficiently edited endogenous dsRNA persistently stimulates MDA5. Genetic intervention targeting MDA5 markedly alleviates some of the inflammatory phenotypes caused by ADAR1 deficiency, indicating that restriction of aberrant MDA5 recognition of self-RNA is an important physiological function of ADAR1.
2.2 PKR–eIF2α Signaling and Translational Stress
(1) PKR Activation
Protein kinase R (PKR; EIF2AK2) can bind directly to dsRNA. Upon binding, PKR undergoes dimerization and autophosphorylation to form an active kinase.
(2) eIF2α Phosphorylation
Activated PKR subsequently phosphorylates the eukaryotic translation-initiation factor eIF2α, suppressing global protein translation and initiating the integrated stress response. Persistent and intense PKR activation can restrict tumor-cell proliferation and survival.
(3) Differences from MDA5 Output
MDA5 primarily converts dsRNA recognition into interferon and inflammatory transcription, whereas PKR acts more directly on protein translation. Following loss of ADAR1 function, both pathways can be released simultaneously, causing tumor cells to mount an innate immune response while also undergoing translational and survival stress.
2.3 The OAS–RNase L Pathway
(1) OAS Activation
Oligoadenylate synthetase (OAS) detects dsRNA and catalyzes the production of 2′-5′-linked oligoadenylates.
(2) RNase L-Mediated RNA Degradation
The resulting 2′-5′ oligoadenylates activate RNase L, promoting the degradation of cellular and viral RNAs, altering RNA homeostasis, and amplifying nucleic acid stress.
(3) Pathway Contributions Differ Across Cellular Contexts
Dependence on the OAS–RNase L pathway varies among cell types. Its actual contribution should be established using genetic interventions targeting OAS or RNase L and cannot be inferred solely from increased RNA degradation.
2.4 ADAR1p150–Z-RNA–ZBP1 Signaling
(1) Z-RNA Recognition
Certain double-stranded nucleic acids can adopt a left-handed Z conformation. ADAR1p150 recognizes Z-RNA through its Zα domain and restricts aberrant activation of innate immune and cell-death signals by Z-conformation nucleic acids.
(2) Release of ZBP1 Signaling
When ADAR1p150 function is reduced or the Zα domain is impaired, Z-RNA is more readily recognized by Z-DNA/RNA-binding protein 1 (ZBP1). ZBP1 contains a RHIM domain that directly connects aberrant nucleic acid sensing to RIPK3.
(3) RIPK3–MLKL Execution
Following the recruitment and activation of RIPK3 by ZBP1, MLKL can undergo phosphorylation, oligomerization, and translocation to the plasma membrane. In cells with an intact RIPK3–MLKL execution system, this process can induce necroptosis.
Table 2. ADAR1-Related Endogenous RNA-Sensing Pathways
Sensing System | Major Signaling Process | Major Output | Changes Following Loss of ADAR1 Function |
MDA5–MAVS | MDA5 recognizes long dsRNA and activates MAVS–TBK1–IRF3 | Type I IFNs and ISGs | Enhanced innate immune and inflammatory transcription |
PKR–eIF2α | dsRNA activates PKR and promotes eIF2α phosphorylation | Translational inhibition and integrated stress response | Reduced protein synthesis and increased cellular stress |
OAS–RNase L | dsRNA activates OAS and induces production of 2′-5′ oligoadenylates | RNase L-mediated RNA degradation | Enhanced RNA stress |
ZBP1–RIPK3–MLKL | ZBP1 recognizes Z-RNA and recruits RIPK3 | Necroptosis and inflammatory output | Increased lytic cell death |
2.5 ADAR1 Deficiency and Autoinflammation
(1) Human Genetic Disorders
Loss-of-function alterations in ADAR1 are associated with autoinflammatory diseases such as Aicardi–Goutières syndrome. Aberrant sensing of self-RNA and persistent type I IFN responses are important pathological features of these disorders.
(2) Animal Phenotypes
Complete loss of Adar in mice causes severe developmental abnormalities and embryonic lethality. Defects in p150 or essential RNA-editing functions similarly produce pronounced inflammatory phenotypes.
(3) Implications for Drug Development
ADAR1 is not a tumor-specific protein. Excessive systemic inhibition may disrupt self-RNA tolerance in normal tissues. Drug development must therefore establish a therapeutic window between antitumor immune activation and inflammatory toxicity in normal tissues.
3 How ADAR1 Promotes Tumor Immune Evasion
3.1 Conditional Dependence of Tumor Cells on ADAR1
(1) High dsRNA Burden
Certain tumors exhibit increased repetitive-element transcription, epigenetic abnormalities, and disrupted nucleic acid homeostasis, resulting in sustained production of endogenous dsRNA. ADAR1 reduces the immunogenicity of these RNAs and prevents persistent activation of innate immunity in tumor cells.
(2) Persistent IFN Environment
IFNs induce ADAR1p150 expression, whereas p150 limits sustained MDA5 and PKR activation by processing endogenous dsRNA. This establishes a negative-feedback loop of elevated IFN, increased ADAR1p150, and reduced RNA immunogenicity.
(3) Expression Does Not Equal Dependence
High ADAR1 expression does not necessarily indicate functional dependence on ADAR1. The endogenous dsRNA burden, basal IFN state, and integrity of downstream systems such as MDA5, PKR, and ZBP1 also determine the response to ADAR1 inhibition.
3.2 ADAR1 Restricts Viral Mimicry
(1) Reactivation of Repetitive Elements
When epigenetically silenced endogenous retroelements are reactivated in tumor cells, their transcripts can generate dsRNA with structural characteristics resembling those of viral RNA.
(2) Viral Mimicry Response
Activation of MDA5, PKR, and type I IFN-related pathways by these endogenous RNAs induces an innate immune state resembling viral infection, a phenomenon known as viral mimicry.
(3) ADAR1 Establishes an RNA-Tolerance Barrier
ADAR1 reduces the immunostimulatory capacity of endogenous dsRNA, allowing tumor cells to buffer viral mimicry responses. Following ADAR1 inhibition, the same amount of endogenous dsRNA can produce a stronger immune output.
3.3 ADAR1 and Immune Checkpoint Blockade
(1) Suppression of Tumor-Intrinsic Immune Signaling
Persistent restriction of immunogenic dsRNA by ADAR1 can reduce IFN, chemokine, and other innate immune signals, decreasing the ability of tumor cells to communicate nucleic acid abnormalities to the immune system.
(2) ADAR1 Deficiency and Increased Sensitivity to ICB
ADAR1 deficiency enhances MDA5- and PKR-mediated dsRNA sensing and increases the response to immune checkpoint blockade in certain tumor models. ADAR1 therefore constitutes an intrinsic innate immune barrier within tumor cells.
(3) Basis for Combination Therapy
ADAR1 targeting primarily enhances tumor-intrinsic immune stimulation and cellular stress, whereas PD-1/PD-L1 blockade primarily relieves suppression of effector T cells. These interventions act at different levels of the immune response and have mechanistically complementary effects.
3.4 ADAR1–ZBP1 Signaling and Immunogenic Cell Death
(1) ZBP1 Activation
When ADAR1p150-mediated protection is reduced, stimulation of ZBP1 by Z-RNA increases. Through its RHIM domain, ZBP1 recruits RIPK3 and directs aberrant nucleic acid sensing into a cell-death program.
(2) Necroptosis
Activated RIPK3 phosphorylates MLKL, promoting MLKL oligomerization and membrane translocation and ultimately increasing plasma membrane permeability and inducing cellular lysis.
(3) Immune Output
Lytic cell death can be accompanied by the release of DAMPs, tumor antigens, and inflammatory signals. Reduced ADAR1 function may therefore not only directly restrict tumor-cell survival but also reshape the local immune microenvironment.
3.5 Coding-Region RNA Editing and Tumor Phenotypes
(1) AZIN1 Editing
ADAR1-mediated editing at specific AZIN1 sites can alter protein properties and has been associated with cellular proliferation, survival, and malignant progression in certain tumors. It represents a characteristic example of coding-region A-to-I editing affecting tumor phenotypes.
(2) Direction of Effects from Different Editing Events
The effects of editing individual coding transcripts depend on the substrate and cellular context. Different editing events may produce distinct or even opposing tumor phenotypes, and not all coding-region editing by ADAR1 can be classified simply as oncogenic.
(3) Principal Focus of Tumor Immunity Research
The main rationale for targeting ADAR1 in tumor immunity remains centered on large-scale editing of endogenous dsRNA, innate immune tolerance, and Z-RNA-related cell death rather than on individual coding-region editing events.
4 ADAR1-Related Cancer Treatment Strategies
4.1 Combination with PD-1/PD-L1 Blockade
(1) Increasing Innate Immune Stimulation
ADAR1 inhibition can release MDA5–MAVS-related signaling and increase IFN and chemokine expression, enabling tumor cells with insufficient immune stimulation to generate more pronounced nucleic acid danger signals.
(2) Enhancing Effector Immunity
PD-1/PD-L1 blockade relieves suppression of effector T cells, allowing the innate immune stimulation induced by ADAR1 inhibition to be more readily converted into a sustained antitumor immune response.
(3) Context Dependence of Combination Effects
The basal IFN state, immune-cell infiltration, MDA5 and PKR function, and the execution capacity of the ZBP1–RIPK3–MLKL pathway may all affect the outcome of combination therapy.
4.2 Combination with Epigenetic Therapy
(1) Increasing Endogenous dsRNA
DNA methyltransferase inhibitors can relieve transcriptional silencing of certain endogenous retroelements, increasing the abundance of repetitive-element RNAs and the endogenous dsRNA burden.
(2) Reducing dsRNA Tolerance
ADAR1 inhibition reduces the editing and immune desensitization of newly generated dsRNA, allowing MDA5, PKR, or ZBP1 to reach their activation thresholds more readily.
(3) Establishing a Dual Intervention
Epigenetic therapy increases the production of immunogenic RNA, whereas ADAR1 inhibition reduces the capacity of tumor cells to process these RNAs. The two mechanisms complement one another at the level of viral mimicry.
4.3 Activation of ZBP1-Related Bypass Pathways
(1) Z-Conformation Nucleic Acid Stress
In addition to directly removing ADAR1-mediated protection, stimulation associated with Z-conformation nucleic acids can be increased to enhance the probability that ZBP1 will engage RIPK3-dependent death signaling.
(2) CBL0137
CBL0137 is a curaxin compound that perturbs FACT-related chromatin function. In ADAR1–ZBP1 research systems, the resulting chromatin and nucleic acid conformational stress can enhance ZBP1-related signaling.
(3) Distinction from Direct ADAR1 Inhibition
CBL0137 is not a direct ADAR1 inhibitor and is more appropriately used as a bypass research tool within the ADAR1–ZBP1 network.
5 Products for ADAR1-Related Mechanistic Research and Experimental Detection
5.1 Core Products for ADAR1 and dsRNA-Sensing Research
Catalog # | Product Name | Grade & Purity | Mechanism of Action/Target | Research Application |
Recombinant ADAR1 Antibody | Recombinant, ExactAb™, Validated, 0.18 mg/mL | Specifically recognizes ADAR1, an A-to-I RNA-editing enzyme, without distinguishing between the p110 and p150 isoforms | ADAR1 expression detection | |
Polyinosinic acid-polycytidylic acid | Moligand™, ≥90% | A synthetic dsRNA analog recognized by RNA sensors such as MDA5, activating MAVS–TBK1–IRF3 and type I IFN-related signaling | dsRNA stress modeling | |
MDA5 | ≥80%(SDS-PAGE) | Recombinant MDA5/IFIH1 protein; MDA5 is a RIG-I-like receptor that recognizes long dsRNA and connects to MAVS through its CARD domains | In vitro protein studies | |
Recombinant MDA5 Antibody | Recombinant, ExactAb™, Validated, KD Validation, See COA | Specifically recognizes MDA5/IFIH1 protein | MDA5 expression detection | |
Human Melanoma Differentiation-associated Protein 5 (MDA5) ELISA Kit | BioReagent | Quantifies MDA5 protein through specific antigen–antibody binding | MDA5 quantification | |
IFIH1 Human Pre-designed siRNA Set A | — | Targets IFIH1 mRNA and reduces MDA5 expression, attenuating long-dsRNA recognition and MAVS signal transduction | Genetic attribution of MDA5 | |
Recombinant RIG-I/DDX58 Antibody | ExactAb™, Validated, Recombinant, 3.0 mg/mL | Specifically recognizes RIG-I/DDX58, another RIG-I-like RNA sensor | RLR-branch control | |
Imidazolo-oxindole PKR inhibitor C16 | Moligand™, ≥98% | Inhibits EIF2AK2/PKR kinase activity and reduces PKR-mediated eIF2α phosphorylation and translational inhibition | Attribution of translational stress | |
OAS1 Human Pre-designed siRNA Set A | — | Targets OAS1 mRNA and reduces OAS1 expression, decreasing 2′-5′ oligoadenylate production and RNase L-related signaling | Attribution of the OAS branch |
5.2 Products for Studying MAVS–TBK1–IRF3 Signaling
Catalog # | Product Name | Grade & Purity | Mechanism of Action/Target | Research Application |
MAVS Human Pre-designed siRNA Set A | — | Targets MAVS mRNA and reduces MAVS expression, interrupting transmission of mitochondrial antiviral signals from RLRs to TBK1–IRF3 | Genetic attribution of MAVS | |
Recombinant Human TBK1 Protein | ≥90%(SDS-PAGE) | Recombinant human TBK1; TBK1 is a serine/threonine kinase that phosphorylates downstream substrates such as IRF3 | In vitro kinase studies | |
Recombinant NAK/TBK1 Antibody | Recombinant, ExactAb™, Validated, See COA | Specifically recognizes total TBK1 without distinguishing its phosphorylation state | TBK1 expression detection | |
Recombinant Phospho-NAK/TBK1 (S172) Antibody | KD Validation | Specifically recognizes TBK1 phosphorylated at Ser172, a site associated with TBK1 kinase activation | TBK1 activation detection | |
TBK1 Human Pre-designed siRNA Set A | — | Targets TBK1 mRNA and reduces TBK1 expression, attenuating IRF3 activation and type I IFN transcriptional output | Genetic attribution of TBK1 | |
TBK1-IN-1 | ≥98% | Inhibits TBK1 kinase activity and reduces IRF3 phosphorylation and downstream type I IFN signaling | Pharmacological rescue of TBK1 signaling | |
Human Phosphorylated TANK Binding Kinase 1 (P-TBK1) ELISA Kit | BioReagent | Quantifies p-TBK1 through specific binding between phosphorylated TBK1 and antibodies | TBK1 activation quantification | |
IRF3 Human Pre-designed siRNA Set A | — | Targets IRF3 mRNA and reduces IRF3 expression, attenuating transcription of TBK1-downstream genes such as IFNB1 | Genetic attribution of IRF3 | |
Recombinant IRF3 Antibody | ExactAb™, Validated, Recombinant, 0.3 mg/mL | Specifically recognizes total IRF3 protein | IRF3 expression detection | |
Human Interferon Regulatory Factor 3 (IRF3) ELISA Kit | BioReagent | Quantifies IRF3 protein through specific antigen–antibody binding | IRF3 quantification |
5.3 Products for Studying IFN–STAT Signaling and ISG Effects
Catalog # | Product Name | Grade & Purity | Mechanism of Action/Target | Research Application |
Human Interferon Beta (IFN-β) ELISA Kit | BioReagent | Quantifies IFN-β through specific cytokine–antibody binding | IFN-β secretion quantification | |
Faralimomab (anti-IFNAR-1) | Carrier Free, Recombinant, ExactAb™, Low Endotoxin, Azide Free, ≥95%(SDS-PAGE&SEC-HPLC) | Binds IFNAR1 and blocks type I IFN receptor-mediated signal transduction, reducing downstream JAK–STAT responses | IFN feedback blockade | |
IFN alpha-IFNAR-IN-1 hydrochloride | Moligand™, ≥98% | Inhibits IFN–IFNAR-related signaling and reduces receptor-dependent STAT-pathway activation | Pharmacological attribution of IFNAR signaling | |
Recombinant Phospho-STAT1 (S727) Antibody | KD Validation | Specifically recognizes STAT1 phosphorylated at Ser727, a site involved in STAT1 transcriptional regulation | STAT1 activation detection | |
Recombinant STAT1 Antibody | Recombinant, ExactAb™, KD Validation, Validated, See COA | Specifically recognizes total STAT1 without distinguishing its phosphorylation state | STAT1 expression detection | |
STAT1 Human Pre-designed siRNA Set A | — | Targets STAT1 mRNA and reduces STAT1 expression, attenuating IFN-induced downstream transcriptional programs | Genetic attribution of STAT1 | |
Recombinant STAT2 Antibody | KO Validation | Specifically recognizes STAT2; STAT2 forms the ISGF3 transcriptional complex with STAT1 and IRF9 | STAT2 expression detection | |
STAT2 Human Pre-designed siRNA Set A | — | Targets STAT2 mRNA and reduces STAT2 expression, interfering with ISGF3 formation and ISG transcription | Genetic attribution of STAT2 | |
Recombinant ISG15 Antibody | Recombinant, ExactAb™, Validated, High Performance, See COA | Specifically recognizes ISG15, a representative interferon-stimulated gene product | IFN-effector readout | |
Human Ubiquitin-like Modifier (ISG15) ELISA Kit | BioReagent | Quantifies ISG15 protein through specific antigen–antibody binding | ISG15 quantification | |
ISG15 Human Pre-designed siRNA Set A | — | Targets ISG15 mRNA and reduces ISG15 expression, attenuating ISG15- and ISGylation-related effects | Functional attribution of ISG15 |
5.4 Products for Studying Viral Mimicry and ZBP1–RIPK3–MLKL Signaling
Catalog # | Product Name | Grade & Purity | Mechanism of Action/Target | Research Application |
5-Aza-2′-deoxycytidine | Moligand™, ≥98% | Inhibits DNA methyltransferase-related processes and reduces DNA methylation, relieving transcriptional silencing of certain repetitive elements and increasing the endogenous dsRNA burden | Enhancement of viral mimicry | |
CBL0137 HCl | 10mM in DMSO | A curaxin-class FACT-modulating compound that perturbs chromatin states and increases stress associated with Z-conformation nucleic acids | ZBP1 bypass modeling | |
GSK872 | Moligand™, ≥98% | Inhibits RIPK3 kinase activity and reduces RIPK3-mediated MLKL activation and necroptotic execution | Rescue at the RIPK3 node | |
Necrosulfonamide | ≥99% | Interferes with human MLKL execution and restricts plasma membrane damage mediated by activated MLKL | Rescue at the MLKL node | |
Necrostatin-1 | Moligand™, ≥99% | Inhibits RIPK1 kinase activity and blocks transmission of classical RIPK1-dependent death signals to RIPK3 | Identification of RIPK1 dependence | |
GSK'963 | Moligand™, ≥98% | Potently inhibits RIPK1 kinase activity and reduces RIPK1 kinase-dependent death-complex signaling | Confirmation of RIPK1-related results | |
7-Cl-O-Nec1 | Moligand™, ≥98% | Inhibits RIPK1 kinase activity and restricts initiation of classical RIPK1-dependent necroptosis | Independent pharmacological control for RIPK1 | |
MLKL-IN-2 | ≥99% | Interferes with MLKL-related execution and reduces terminal plasma membrane damage mediated by MLKL | Confirmation of MLKL-related results | |
Z-VAD(OH)-FMK (Caspase Inhibitor VI) | 10mM in DMSO | Broadly inhibits caspase activity, blocks caspase-dependent apoptosis, and alters competition among certain cell-death pathways | Cell-death modality identification | |
RIP3 Mouse mAb | Carrier Free, ExactAb™, Validated, 0.5 mg/mL | Specifically recognizes total RIPK3 protein | RIPK3 expression detection | |
Recombinant RIP Antibody | Recombinant, ExactAb™, Validated, See COA | Specifically recognizes RIPK1-related protein | RIPK1 expression detection |
ADAR1 connects A-to-I RNA editing, endogenous nucleic acid immune tolerance, and tumor immune evasion. Current targeting strategies have expanded to direct catalytic inhibition, selective intervention against p150, and protein degradation, with compounds such as ADAR1i-124 and Z-PROTACs providing early experimental evidence. Further development will depend on target selectivity, the therapeutic window, and accurate identification of ADAR1-dependent tumors.
References
[1] Liu C, Choi Y. ADAR1: a central regulator of dsRNA sensing in host-virus interactions. Front Immunol. 2026;17:1756517. doi: 10.3389/fimmu.2026.1756517.
[2] Liddicoat BJ, et al. RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. Science. 2015;349(6252):1115-1120.
[3] Pestal K, et al. Isoforms of RNA-Editing Enzyme ADAR1 Independently Control Nucleic Acid Sensor MDA5-Driven Autoimmunity and Multi-organ Development. Immunity. 2015;43(5):933-944.
[4] Chung H, et al. Human ADAR1 Prevents Endogenous RNA from Triggering Translational Shutdown. Cell. 2018;172(4):811-824.e14.
[5] Li Y, et al. Ribonuclease L mediates the cell-lethal phenotype of double-stranded RNA editing enzyme ADAR1 deficiency in a human cell line. eLife. 2017;6:e25687.
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