ifn-a-1

IFN alpha-IFNAR-IN-1 hydrochloride is an inhibitor of the interaction between IFN-α and IFNAR, effectively inhibiting MVA-induced IFN-α responses by BM-pDCs with an IC50 of 2-8 μM.

StA-IFN-1 is an inhibitor of the interferon (IFN) induction pathway with an IC50 value of 4.1 μM in a GFP reporter assay for IFN induction similar to TPCA-1 , which specifically inhibits the IKKβ component of the IFN induction pathway. It does not show inhibitory activity in a GFP reporter assay for IFN signaling in which ruxolitinib , which is specific for the IFN signaling component JAK1, is active. StA-IFN-1 reduces the levels of IFN-β, but not ISG MxA, mRNA, suggesting that it is selective for the IFN induction pathway and not the IFN signaling pathway.

IFN-α Receptor Recognition Peptide 1, associated with receptor interactions, is a peptide of IFN-α.

IFN alpha-IFNAR-IN-1 is a nonpeptidic, low-molecular-weight inhibitor that disrupts the interaction between IFN-α and IFNAR, inhibiting MVA-induced IFN-α responses by BM-pDCs (IC50: 2-8 μM).

IFN-γ Antagonist 1 (AYCRDGKIGPPKLDIRKEEKQI), an interferon γ (IFN γ) antagonist, effectively inhibits IFN-γ induced HLR/DR antigen expression in Colon 205 cells, demonstrating an IC50 of approximately 35 μM. This compound shows promise for applications in immune regulation [1].

IFN-γ Antagonist 1 (AYCRDGKIGPPKLDIRKEEKQI) acetate, an interferon γ (IFN γ) antagonist, effectively inhibits the expression of HLR DR antigen in Colon 205 cells induced by IFN-γ, with an IC50 of approximately 35 μM. This compound holds promise for applications in immune regulation [1].

Deucravacitinib (BMS-986165) inhibits IL-12/23 and type I IFN pathways[1][2]. BMS-986165 is a highly selective, orally bioavailable allosteric TYK2 inhibitor for the treatment of autoimmune diseases. Which selectively binds to TYK2 pseudokinase (JH2) domain (IC50=1.0 nM) and blocks receptor-mediated Tyk2 activation by stabilizing the regulatory JH2 domain.

TNF/IFNγ-IN-1 (TGA) is a dual inhibitor of TNF and IFN-γ. TNF/IFNγ-IN-1 has potential antioxidant and anti-inflammatory activities for neurodegenerative diseases such as Alzheimer.

T6167923 is a potent, selective inhibitor of MyD88-dependent signaling pathways. It achieves this by directly binding to the Toll/IL1 receptor (TIR) domain of MyD88, preventing MyD88 homodimer formation. Subsequently, T6167923 impedes NF-κB driven Staphylococcus enterotoxin AP (SEAP) activity and boasts improved anti-inflammatory effects, with IC50s values of 2.7 μM for IFN-γ, 2.9 μM for IL-1β, and 2.66 μM each for IL-6 and TNF-α, demonstrating its efficacy across multiple inflammatory mediators [1].

Interferon receptor inducer-1 Used in the treatment of a disorder in which the induction of interferon is involved. is an interferon (IFN) receptor inducer.

Fontolizumab (HuZAF) is a humanized monoclonal antibody targeting IFN-gamma, functioning as an immunosuppressive agent and utilized in the study of Crohn’s disease [1].

STING agonist 1a is an agonist of stimulator of interferon genes (STING).1It induces expression of an IRF-inducible SEAP reporter gene in a cell-based assay (EC50= 16.77 μM). STING agonist 1a (12.5-100 μM) induces expression of IFN-β, IL-6, and chemokine (C-X-C motif) ligand 10 (CXCL10) in THP-1 cells, an effect that can be reversed by STING knockout or the STING inhibitor H-151 . 1.Hou, H., Yang, R., Liu, X., et al.Discovery of triazoloquinoxaline as novel STING agonists via structure-based virtual screeningBioorg. Chem.100103958(2020)

PROTAC IDO1 Degrader-1, a pioneering compound, efficiently targets indoleamine 2,3-dioxygenase 1 (IDO1) for ubiquitination and degradation by recruiting IDO1 to the CRBN E3 ligase, thereby facilitating its entry into the ubiquitin-proteasome system (UPS) with a DC50 of 2.84 μM. This compound also moderately enhances the tumor-killing efficacy of HER2 CAR-T cells[1].

GSK2245035 is a highly selective intranasal TLR7 agonist with preferential Type-1 interferon (IFN)-stimulating properties (pEC50s: 9.3 and 6.5 for IFNα and TFNα). It effectively suppresses allergen-induced Th2 cytokine production in human peripheral blood

PCC0208018 is a novel activator of effector T cells, enhancing T cell proliferation and activation to release interferon gamma (IFN-γ) and interleukin-2 (IL-2) without blocking the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) binding and not directly affecting tumor cell viability in vitro.

STING agonist-23 (CF502) is a non-nucleotide, small-molecule stimulator of the STING pathway. Upon activation, it enhances the phosphorylation of STING, TBK1, and IRF3, leading to elevated levels of IFN-β, IL-6, CXCL-10, TNF-α, ISG-15, and CCL-5 in tumor cells. Moreover, STING agonist-23 demonstrates efficacy against SARS-CoV series strains [1].

STING agonist-23 (CF505) is a non-nucleotide, small-molecule compound that stimulates STING, enhancing the phosphorylation of STING, TBK1, and IRF3. It elevates the production of IFN-β, IL-6, CXCL-10, TNF-α, ISG-15, and CCL-5 in tumor cells and demonstrates efficacy against SARS-CoV strains [1].

VISTA-IN-3 (Compound A4), a potent small molecule inhibitor of VISTA, exhibits a dissociation constant (K D) of 0.49 μM. This compound effectively induces the release of IFN-γ cytokines and demonstrates synergistic enhancement of anti-cancer activity when combined with PD-L1 antibody [1].

Ropeginterferon alfa-2b (Ropeginterferon alfa-2b-njft), a monopegylated interferon-alpha (IFN-α), is used in the study of myeloproliferative neoplasms [1].

Cetrelimab (JNJ 63723283; JNJ 3283), a humanized IgG4κ monoclonal antibody targeting PD-1, binds to PD-1 (Kd=1.72 nM, HEK293) to prevent interaction with PD-L1 and PD-L2 (IC50s=111.7 ng mL and 138.6 ng mL, respectively), stimulating peripheral T cells, elevating IFN-γ, IL-2, and TNF-α levels, and inhibiting tumor growth in vivo [1].

PD-1 PD-L1-IN-31 is a potent inhibitor of PD-1 PD-L1 (IC50=2.2 nM) that enhances IFN-γ secretion and activates the immune response of peripheral blood mononuclear cells (PBMCs), leading to the inhibition of tumor cells [1].

BDW568, a prodrug of BDW-OH, serves as a stimulator of interferon genes (STING) agonist. This compound effectively induces STING transcriptional activity, evidenced by a reporter assay in THP-1 cells, with an EC50 value of 7.6 µM. Furthermore, at a concentration of 50 µM, BDW568 prompts phosphorylation of TANK-binding kinase 1 (TBK1) and IFN regulatory factor 3 (IRF3) within THP-1 cells, showcasing its biochemical activity in cellular signaling pathways.

AJ2-71 is a SLC15A4 inhibitor that suppresses IFN-α production and obstructs SLC15A4-mediated MDP transport, making it suitable for research of inflammation [1].

NG 25 is a type II kinase inhibitor that inhibits MAP4K2 and TAK1 (IC50s = 21.7 and 149 nM, respectively).1It also inhibits the Src family kinases Src and LYN (IC50s = 113 and 12.9 nM, respectively) and Abl family kinases (IC50s = 75.2 nM), as well as CSK, FER, and p38α (IC50s = 56.4, 82.3, and 102 nM, respectively). NG 25 (100 nM) prevents TNF-α-induced IKKα/β phosphorylation and IκB-α degradation in L929 cells. It inhibits secretion of IFN-α and IFN-β induced by CpG type B and CL097, respectively, in Gen2.2 cells in a concentration-dependent manner.2NG 25 decreases cell viability of HCT116KRASWT, and to a greater degree of HCT116KRASG13D, colorectal cancer cells in a concentration-dependent manner.3It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26KRASG12Dmouse orthotopic model of colorectal cancer. 1.Tan, L., Nomanbhoy, T., Gurbani, D., et al.Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2)J. Med. Chem.58(1)183-196(2015) 2.Pauls, E., Shpiro, N., Peggie, M., et al.Essential role for IKKβ in production of type 1 interferons by plasmacytoid dendritic cellsJ. Biol. Chem. 287(23)19216-19228(2012) 3.Ma, Q., Gu, L., Liao, S., et al.NG25, a novel inhibitor of TAK1, suppresses KRAS-mutant colorectal cancer growth in vitro and in vivoApoptosis24(1-2)83-94(2019)

5-epi-Arvestonate A, a sesquiterpenoid extracted from Seriphidium transiliense whole plants, enhances melanogenic production by stimulating MITF and tyrosinase family gene transcription. Additionally, it suppresses IFN-γ-chemokine expression via the JAK/STAT signaling pathway in HaCaT cells [1].

ODN 6016, a CpG-A oligonucleotide, shows potential in inducing IFN-α production, primarily for studying immune disorders such as immunodeficiency due to HIV-1. Its sequence is T-sp-C-G-A-C-G-T-C-G-T-G-G-sp-G-sp-G-sp-G [1] [2].

ODN D-SL03, a class C CpG oligonucleotide, effectively stimulates peripheral blood mononuclear cells (PBMCs) to produce high levels of IFN-α. It activates human B cells, NK cells, and mononuclear cells, elevating the expression of CD80, CD86, and HLA-DR on PBMC subsets' surface. Additionally, ODN D-SL03 impedes tumor growth. Its sequence: 5'-tcgcgaacgttcgccgcgttcgaacgcgg-3' [1].

STING18 is a competitive ligand of stimulator of interferon genes (STING; IC50 = 0.068 μM in a radioligand binding assay).1 It inhibits cGAMP-induced IFN-β production (IC50 = 11 μM) but does not stimulate IFN-β production (EC50 = >30 μM) in THP-1 cells. |1. Siu, T., Altman, M.D., Baltus, G.A., et al. Discovery of a novel cGAMP competitive ligand of the inactive form of STING. Med. Chem. Lett. 10(1), 92-97 (2019).

BRD0476 is a suppressor of pancreatic β-cell apoptosis. BRD0476 inhibits interferon-gamma (IFN-γ)-induced Janus kinase 2 (JAK2) and signal transducer and activation of transcription 1 (STAT1) signaling to promote β-cell survival. BRD0476 inhibits JAK-STAT

Interferon alfa, a type I interferon, activates new genes, displaying strong antiviral and antiproliferative effects on target cells. It signals through receptor-mediated activation of Stat1 and Stat2, which heterodimerize into a STAT complex binding with the DNA-binding protein IRF-9 (p48) to form ISGF-3 (IFN-stimulated gene factor 3). This complex further activates driver genes to fulfill its antiviral role [1].

MAO A HSP90-IN-2 (compound 4-C), a dual inhibitor of HSP90 and MAO A, exhibits IC50 values of 0.016 μM for MAO A and 4.58 μM for HSP90. This compound enhances HSP70 expression, diminishes HER2 and phospho-Akt levels, downregulates IFN-γ-induced PD-L1 expression in GL26 cells, and demonstrates efficacy against Temozolomide-sensitive and -resistant GBM cells, colon cancer, leukemia, and non-small cell lung cancer, possibly impeding tumor immune evasion [1].

SIMR3030, a potent inhibitor of SARS-CoV-2 PLpro, possesses an IC50 of 0.0399 µg mL and demonstrates antiviral activity by diminishing the expression of SARS-CoV spike, ORF1b, IFN-α, and IL-6 mRNA. Additionally, SIMR3030 has been shown to have a satisfactory safety profile in mice [1].

STING agonist C11 is an agonist of the stimulator of interferon genes (STING) pathway.1 It induces secretion of type I IFN from THF and MM6 cells when used at a concentration of 50 μM. STING agonist C11 induces phosphorylation of IFN regulatory factor 3 (IRF3) and increases expression of IFIT1 and viperin, but not IL-1β, IL-6, or IL-8 in THF cells in a STING-dependent manner. It reduces viral titers of chikungunya, Venezuelan equine encephalitis, o'nyong-nyong, Mayaro, and Ross River viruses grown in THF cells (EC90s = 16.44, 16.7, 18.84, 25.19, and 22.57 μM, respectively), an effect that is dependent on the presence of STING and the IFN-α/β receptor (IFNAR).References1. Gall, B., Pryke, K., Abraham, J., et al. Emerging alphaviruses are sensitive to cellular states induced by a novel small-molecule agonist of the STING pathway. J. Virol. 92(6), e01913-01917 (2018). STING agonist C11 is an agonist of the stimulator of interferon genes (STING) pathway.1 It induces secretion of type I IFN from THF and MM6 cells when used at a concentration of 50 μM. STING agonist C11 induces phosphorylation of IFN regulatory factor 3 (IRF3) and increases expression of IFIT1 and viperin, but not IL-1β, IL-6, or IL-8 in THF cells in a STING-dependent manner. It reduces viral titers of chikungunya, Venezuelan equine encephalitis, o'nyong-nyong, Mayaro, and Ross River viruses grown in THF cells (EC90s = 16.44, 16.7, 18.84, 25.19, and 22.57 μM, respectively), an effect that is dependent on the presence of STING and the IFN-α/β receptor (IFNAR). References1. Gall, B., Pryke, K., Abraham, J., et al. Emerging alphaviruses are sensitive to cellular states induced by a novel small-molecule agonist of the STING pathway. J. Virol. 92(6), e01913-01917 (2018).

STING agonist-23 (CF508), a non-nucleotide small-molecule STING agonist, activates STING, thereby enhancing the phosphorylation of STING, TBK1, and IRF3. This activation elevates the production of IFN-β, IL-6, CXCL-10, TNF-α, ISG-15, and CCL-5 in tumor cells. Moreover, STING agonist-23 demonstrates efficacy against SARS-CoV series strains [1].

STING agonist-23 (CF510) is a non-nucleotide, small-molecule activator of the STING pathway. It initiates the phosphorylation of STING, TBK1, and IRF3, enhancing the production of IFN-β, IL-6, CXCL-10, TNF-α, ISG-15, and CCL-5 in tumor cells. Notably, it demonstrates activity against SARS-CoV series strains [1].

ODN 21595, a guanine-modified inhibitor targeting TLR7 and TLR9, effectively inhibits the release of IFN-α and IL-6 without exhibiting cytotoxicity. It also reduces the expression of CD86 and HLA-DR, showcasing potential for systemic lupus erythematosus (SLE) research [1].

MSA-2 dimer, a selective and orally active non-nucleotide STING agonist with a dissociation constant (Kd) of 145 μM, demonstrates prolonged antitumor and immunogenic activity. It non-covalently binds to STING as a dimer, showing greater permeability compared to cyclic dinucleotide[1].

CAY10748 is an agonist of stimulator of interferon genes (STING; IC50= 0.3794 μM in a competition binding assay).1It activates STING in STING-expressing, but not STING knockout, THP-1 cells (EC50s = 0.287 and >100 μM, respectively, in a reporter assay). It induces phosphorylation of STING at the serine in position 366, as well as phosphorylation of TBK1 and IFN regulatory factor 3 (IRF3), indicating activation of the STING-TBK1-IRF3 signaling pathway. CAY10748 increases the secretion of IFN-β and the levels of chemokine (C-X-C motif) ligand 10 (CXCL10), and IL-6 in peripheral blood mononuclear cells (PBMCs) when used at a concentration of 10 μM. It also reduces tumor growth in a CT26 murine colon cancer model when administered at a dose of 0.15, but not 1.5, mg/kg. 1.Xi, Q., Wang, M., Jia, W., et al.Design, synthesis, and biological evaluation of amidobenzimidazole derivatives as stimulator of interferon genes (STING) receptor agonistsJ. Med. Chem.63(1)260-282(2019)

AX-024 is a novel chemical compound that acts as an orally available inhibitor of the TCR-Nck interaction. Its primary mechanism of action is the selective inhibition of T cell activation triggered by TCR stimulation. With an IC50 value of approximately 1 nM, AX-024 effectively modulates cell signaling by specifically targeting SH3 domains. Additionally, AX-024 demonstrates desirable characteristics such as low acute toxicity, high potency, and excellent selectivity. Notably, it exhibits strong inhibitory effects on the production of IL-6, TNF-α, IFN-γ, IL-10, and IL-17A.

Through its effects on ULK1 and ULK2, MRT67307 blocks autophagy. MRT67307 prevents the phosphorylation of IRF3 and the production of IFN-β and increases toll-like receptor-induced IL-10 and IL-1ra secretion in macrophages. MRT67307 is a kinase inhibitor that has been shown to inhibit TBK1, MARK1-4, IKKε, and NUAK1 (IC50 values are 19, 27-52, 160, and 230 nM, respectively), the salt-inducible kinases (SIKs; IC50s =250, 67, and 430 nM for SIK1, SIK2, and SIK3, respectively) and ULK1 and ULK2 (IC50s = 45 and 38 nM, respectively).

9c(i472) is an inhibitor of 15-lipoxygenase-1 (15-LO-1; IC50 = 0.19 μM).1 It decreases LPS- and IFN-γ-induced NF- B activity in RAW-Blue cells when used at concentrations of 0.2, 1, and 5 μM. 9c(i472) reduces LPS- and IFN-γ-induced increases in Nos2 expression and lipid peroxidation in RAW 264.7 cells when used at a concentration of 5 μM.

Cobaltic Protoporphyrin IX chloride (CoPP) is a potent heme oxygenase 1 (HO-1) inducer with antiviral activity that inhibits influenza A virus (IAV) infection by inducing a type I IFN response. mTOR inhibitor-8 is a potent mTOR inhibitor and autophagy inducer with antiviral and antitumor activities.

Jaceosidin has anti-oxidative activity. Jaceosidin has anti-inflammatory activity, also a microglial inhibitor with anti-neuroinflammation activity. aceosidin has anticancer activity, modulates the ERK ATM Chk1 2 pathway, leading to inactivation of the Cd

STING agonist 12L is a stimulator of interferon genes (STING) agonist that exhibits binding affinity for both wild-type STING and its variants R232, AQ, and Q with half-maximal inhibitory concentrations (IC50s) of 1.15 µM for wild-type, 1.06 µM for R232, 0.61 µM for AQ, and 1.12 µM for Q. It effectively induces reporter gene expression in THP-1 and RAW 264.7 cells, with half-maximal effective concentrations (EC50s) of 0.38 µM and 12.94 µM, respectively. At a concentration of 5 µM, STING agonist 12L escalates the expression of IFNB1, CXCL10, and IL6 mRNA in THP-1 cells. When administered in vivo at a dose of 10 mg/kg, it enhances plasma IFN-β levels and considerably reduces tumor volume and the number of lung metastases in a B16/F10 murine melanoma model.

6(5H)-Phenanthridinone is an inhibitor of poly(ADP-ribose) polymerase 1 (PARP1) and PARP2. It decreases radiation-induced PARP activity and proliferation of RDM4 murine lymphoma cells. 6(5H)-Phenanthridinone reduces NF-κB-induced transcription of the genes encoding TNF-α, IL-2, and IFN-γ in rat lymphocytes. In vivo, 6(5H)-phenanthridinone reduces spinal cord expression of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, IL-2, and IFN-γ and reduces disease score in a rat model of experimental autoimmune encephalomyelitis (EAE). It also decreases serum levels of lactate dehydrogenase as well as hepatic lipid peroxidation, oxidative DNA damage, and PARP levels.

Ganglioside GM1 asialo is a component of cellular lipid rafts and can be formed by the cleavage of the sialic acid residue from ganglioside GM1 by neuraminidase. Ganglioside GM1 asialo is a glycolipid receptor for P. aeruginosa flagellin and stimulates defensive responses in host cells, including extracellular ATP release, calcium mobilization, and ERK1/2 phosphorylation when stimulated by flagellin and an anti-ganglioside GM1 asialo antibody. The percentage of ganglioside GM1 asialo-positive natural killer (NK) and CD8+ T cells in lung is increased in a mouse model of respiratory syncytial virus (RSV) infection compared with healthy animals. Depletion of ganglioside GM1 asialo-positive NK and T cells reduces IFN-γ levels in the lung, reduces weight loss, and increases lung viral load in RSV-infected mice. Ganglioside GM1 asialo mixture contains ganglioside GM1 asialo molecular species with C18:1 and C20:1 sphingoid backbones.

STING Agonist-22 (CF501) is a potent non-nucleotide STING agonist that functions as an adjuvant by activating STING to induce the type I interferon (IFN-I) response and the production of proinflammatory cytokines. It enhances the efficacy of original protein vaccines by providing potent, broad, and long-term immune protection. Additionally, STING Agonist-22 has applications in research on SARS-CoV-2 variants and sarbecovirus diseases [1].

STING agonist-24 (CF504), a non-nucleotide small-molecule STING agonist, activates STING, leading to increased phosphorylation of STING, TBK1, and IRF3. It elevates levels of IFN-β, IL-6, CXCL-10, TNF-α, ISG-15, and CCL-5 in tumor cells, demonstrating activity against SARS-CoV series strains [1].

Deucravacitinib HCl is a Highly Potent and Selective Allosteric Inhibitor of TYK2. BMS-986165 Blocks Il-12, IL-23 and type I Interferon Signaling and Provides for Robust Efficacy in Preclinical Models of Inflammatory Bowel Disease. MS-986165 potently binds to the Tyk2 pseudokinase domain (Ki = 0.02 nM), and is highly selective against a panel of 265 kinases and pseudokinases. The compound potently inhibited IL-23-, IL-12-, and Type I interferon-driven cellular signaling and transcriptional responses (IC50 range 2-14 nM).