irf3

SU0268 是有效的 8-8-氧鸟嘌呤 DNA 糖基化酶1的选择性抑制剂，具有调控铜绿假单胞杆菌感染免疫反应的能力。

Cridanimod (10-carboxymethyl-9-acridanone, CMA) 是一种是小分子免疫调节剂和干扰素诱导剂，是一种孕酮受体激活剂，能够诱导 IFNα和IFNβ的表达，显著增加 PR 的表达。

CCCP (Carbonyl Cyanide m-Chlorophenylhydrazone) 是一种氧化磷酸化 (OXPHOS) 抑制剂，线粒体质子载体解偶联剂。CCCP 抑制 STING 及其下游信号分子 TBK1 和 IRF3 的激活。

GSK-690693 是一种泛 Akt 抑制剂，对 Akt1、Akt2和 Akt3的 IC50分别为 2 nM、13 nM 和9 nM。它也是一种 AMPK 的抑制剂，影响 ULK1 的活性，并能显著抑制 STING 依赖的 IRF3 的激活。

MRT67307 是一种IKKε和TBK-1的双抑制剂，IC50分别为 160 和 19 nM。它抑制细胞自噬，也可抑制ULK1和ULK2，IC50分别为 45 和 38 nM。

ADU-S100 (MIW815)是一种环二核苷酸(CDN)类的STING激动剂，可显著诱导IFN-β和促炎细胞因子TNF-α、IL-6、MCP-1的产生，诱导TBK1和IRF3磷酸化，具有抗肿瘤作用。

c-di-AMP (Cyclic diadenylate) is a STING agonist. It binds to the transmembrane protein STING thereby activating the TBK3-IRF3 signaling pathway.

KIN1408是一种抗病毒的小分子化合物，是RIG-1样 受体 (RLR) 途径的激动剂，能够驱动IRF3（干扰素调节因子 3）激活以诱导先天免疫基因（如 MDA5、RIG-1、Mx1、IRF7 和 IFIT1）表达，也能够通过靶向 MAVS（线粒体抗病毒信号蛋白）或其上游因子，促进 IRF3 的核转位。亲本为KIN1400，同为衍生物的还有KIN1409，

KIN1400, a novel IRF3 activator, triggers IRF3-dependent innate immune antiviral genes and IFNbeta307 expression, suppresses WNV, DV infection, and HCV replication.

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)

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).

TBK1 IKKε-IN-4 is a 6-aminopyrazolopyrimidine derivative and a potent, selective TBK1 and IKKε inhibitor with IC50 values of 13 nM and 59 nM, respectively. TBK1 IKKε-IN-4 shows 100- to 1000-fold less activity against other protein kinases including PDK1, PI3K family members and mTOR[1]. TBK1 IKKε-IN-4 (Compound II; 96 hours; A549 andHCC44 cells) treatmentdisplays selective toxicity in TBK1-dependent cancer cell lines (IC50 of ~ 4.2 μM for H441 cells and IC50 of ~0.4 μM for A549 cells)[1].TBK1 IKKε-IN-4 (Compound II; 0-2 μM; 30 minutes; HCC44 cells) treatment inhibits the AKT activity[1].TBK1 IKKε-IN-4 (Compound II) inhibits LPS-induced expression of IFNβ (IC50 =62 nM), and the IFNβ target genes IP10 (IC50 =78 nM) and Mx1 (IC50=20 nM). TBK1 IKKε-IN-4 effectively blocksTLR3-dependent IRF3 nuclear translocation in cells with an IC50 under 100 nM, but does not impair TNFR1-dependent p65 NFκB nuclear translocation with doses as high as 20 μM[1]. [1]. Ou YH, et al. TBK1 directly engages Akt PKB survival signaling to support oncogenic transformation. Mol Cell. 2011 Feb 18;41(4):458-70.

KIN1148 是一种新型小分子佐剂，是IRF3激动剂，用于增强流感疫苗效率。

STINGmodulator-4 是一种竞争性的 STING 调节剂，对 R232HSTING 的 Ki 为 0.0933 μM。STINGmodulator-4 在 THP-1 细胞中对 p-IRF3 的 EC50为 >10 μM。

c-di-AMP (Cyclic diadenylate) sodium 作为一种STING 激动剂，通过结合STING 激活TBK3-IRF3 信号途径，引发I 型 IFN 和 TNF 产生，兼具细菌第二信使功能，在革兰氏阳性细菌中调控细胞生长、存活及毒力，并影响宿主免疫反应。此外，作为有效的粘膜佐剂，它能刺激体液和细胞反应。

STINGagonist-23 (CF502) 是一种非核苷酸小分子 STING 激动剂。STINGagonist-23 激活 STING，增加 STING、TBK1和 IRF3的磷酸化。STINGagonist-23 可促进肿瘤细胞中 IFN-β、IL-6、CXCL-10、TNF-α、ISG-15和 CCL-5的水平。STINGagonist-23 表现出抗 SARS-CoV 系列的活性。

STINGagonist-24 (CF504) 是一种非核苷酸小分子STING 激动剂。STINGagonist-23 激活STING，增加STING、TBK1和IRF3的磷酸化。STINGagonist-23 可促进肿瘤细胞中IFN-β、IL-6、CXCL-10、TNF-α、ISG-15和CCL-5的水平。STINGagonist-23 表现出抗SARS-CoV 系列的活性。

STINGagonist-25 (CF505) 是一种非核苷酸小分子 STING 激动剂。STINGagonist-23 激活 STING，增加 STING、TBK1和 IRF3的磷酸化。STINGagonist-23 可促进肿瘤细胞中IFN-β、IL-6、CXCL-10、TNF-α、ISG-15和CCL-5的水平。STINGagonist-23 表现出抗SARS-CoV 系列的活性。

STINGagonist-26 (CF508) 是一种非核苷酸小分子STING 激动剂。STINGagonist-23 激活STING，增加STING、TBK1和IRF3的磷酸化。STINGagonist-23 可促进肿瘤细胞中IFN-β、IL-6、CXCL-10、TNF-α、ISG-15和CCL-5的水平。STINGagonist-23 表现出抗SARS-CoV 系列的活性。

STINGagonist-28 (CF510) 是一种非核苷酸小分子STING 激动剂。STINGagonist-23 激活STING，增加STING、TBK1和IRF3的磷酸化。STINGagonist-23 可促进肿瘤细胞中IFN-β、IL-6、CXCL-10、TNF-α、ISG-15和CCL-5的水平。STINGagonist-23 表现出抗SARS-CoV 系列的活性。

STING-IN-7（化合物 21），作为一种STING抑制剂，具有11.5 nM的IC50值，能够抑制STING与干扰素调节因子 3 (IRF3) 的磷酸化。

Anti-inflammatory agent 65（compound 29）是一种从常春藤酸衍生且具有有效抗炎活性的化合物。它能够抑制一氧化氮（NO）的释放，阻止IRF3和p65的核转位，破坏STING IRF3 NF-κB信号通路，有效减弱炎症反应。

STING激动剂D61（D61）是干扰素基因刺激剂(STING)的激动剂。它在基于细胞的分析中诱导IFN3诱导的分泌性碱性磷酸酶(SEAP)报告基因和IFN-β诱导的报告基因的表达（EC50分别为52.9和116 nM）。D61（4, 6, 和8 µM）增加了编码IFN-β和化学因子（C-X-C基序）配体10（CXCL10）的mRNA的表达以及TANK结合激酶1（TBK1）、IRF3和STING在THP-1单核细胞中的磷酸化。在体内，D61（每隔一天0.25 mg/kg）在CT26小鼠结肠癌模型中减少肿瘤体积，而不影响体重。

BDW568是一种刺激素干扰素基因（STING）的激动剂，同时是BDW-OH的前药形式。在使用THP-1细胞的报告基因测定中，它能诱导STING转录活性（EC50 = 7.6 µM）。BDW568（50 µM）在THP-1细胞中诱导TANK结合激酶1（TBK1）和IFN调节因子3（IRF3）的磷酸化。