il 15

IL-15-IN-1是一种 IL-15依赖性细胞的选择性抑制剂(IC50:0.8 μM)。

Y-320 是一种免疫调节剂，能阻碍IL-15刺激CD4 T 细胞后的IL-17的产生，IC50=20~60 nM。

Isomucronulatol 7-O-beta-glucoside 具有潜在的抗炎活性，在体外对 LPS 刺激产生的 IL-12 p40 表现出微弱的抑制作用。

Nanrilkefusp alfa (SO-C101; SOT101) 是一种选择性的强效融合蛋白，由IL-15和IL-15Rαsushi+结构域组成。该化合物通过增殖和激活记忆性 CD8+T 细胞、自然杀伤细胞、γ δ T 细胞及自然杀伤 T 细胞，有效抑制肿瘤。在多种小鼠肿瘤模型中，Nanrilkefusp alfa 显著抑制肿瘤生长并防止黑色素瘤的远处转移。

PROTACBTK Degrader-6 (Compound 15) 为PROTACBTK类降解剂，其DC50为3.18 nM。该化合物展现出抗炎特性，能够抑制NF-κB的激活，并降低促炎细胞因子（如IL-1β、IL-6）的表达。

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-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。

Ordesekimab (AMG 714) 是一种人 IgG1κ 抗 IL-15 (Interleukin Related) 单克隆抗体。Ordesekimab 竞争性与 IL-15 结合，会抑制 IL-15 与 IL-2Rβ 和 IL-15 受体复合物的共同 γ 链的相互作用，却不与 IL-15Rα 链发生反应。Ordesekimab 可用于研究无反应性乳糜泻 (NRCD) 。

NLRP3-IN-15 是一种有效的、选择性的 NLRP3炎症小体抑制剂 (KD: 5.87 μM)。NLRP3-IN-15 抑制 IL-1β 释放，IC50为 0.131 μM。NLRP3-IN-15可用于炎症研究。

CDK8-IN-15 (Compound 46) 作为一种高效CDK8抑制剂，具有57 nM的IC50值。该化合物能增进CDK8的热稳定性，同时抑制NF-κB，并选择性地抑制CDK家族和酪氨酸。CDK8-IN-15在体外TNF-α诱导的牛皮癣模型中表现出积极效果，能通过增强Foxp3与IL-10的表达来抑制炎症反应，有望在牛皮癣疾病研究中发挥重要作用。

Givinostat (ITF-2357) is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat (ITF2357) suppresses total LPS-induced IL-1β production robustly compared with the reduction by ITF3056. At 25, 50, and 100 nM, Givinostat reduced IL-1β secretion more than 70%. Givinostat (ITF-2357) suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as the combination of IL-12 plus IL-18. IL-6 secretion decreases to 50% at 50 nM Givinostat, but at 100 and 200 nM, there is no reduction[1]. As shown by the CCK-8 assay, Givinostat (ITF-2357) inhibits JS-1 cell proliferation in a concentration-dependent manner. Treatment with Givinostat ≥500 nM is associated with significant inhibition of JS-1 cell proliferation (P<0.01). Also, the cell inhibition rate significantly differs between the group cotreated with Givinostat ≥250 nM plus LPS and the group without LPS treatment (same Givinostat concentration) (P<0.05)[2]. Givinostat (ITF2357) at 10 mg kg is used as a positive control and, as expected, reduced serum TNFα by 60%. Strikingly, pretreatment of ITF3056 starting at 0.1 mg kg significantly reduces the circulating TNFα by nearly 90%. To achieve a significant increase in serum IL-1β production, a higher dose of LPS is injected (10 mg kg), and blood is collected after 4 h. Similarly, when pretreated with lower doses of Givinostat (ITF-2357) (1 or 5 mg kg), there is a 22% reduction for 1 mg kg and 40% for 5 mg kg[1]. [1]. Li S, et al. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem. 2015 Jan 23;290(4):2368-78. [2]. Wang YG, et al. Givinostat inhibition of hepatic stellate cell proliferation and protein acetylation. World J Gastroenterol. 2015 Jul 21;21(27):8326-39. [3]. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12):1-15.

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。

COX-2 15-LOX-IN-4（compound 5i）是一种针对COX-2和15-LOX的双重抑制剂，其IC50值分别为0.075 μM和1.97 μM。该化合物能有效地阻止LPS诱发的细胞内促炎细胞因子（IL-6, ROS）的产生，表现出明确的抗炎活性。

PDE1-IN-5 (Compound 10c) 是一种PDE1C选择性抑制剂，IC50为15 nM。该化合物显示出抗炎活性，能够抑制LPS诱导的iNOS、TNF-α、IL-1α、IL-1β和IL-6表达。在DSS诱导的结肠炎小鼠模型中，PDE1-IN-5对抗炎性肠病(IBD)表现出治疗潜力，并可用于IBD相关研究。

F1是一种抗炎肽，由HIV-1 Tat蛋白质转导域与对应于抑制因子NF-κB激酶-相互作用肽（IKIP）46-60残基的15氨基酸肽链接而成。在5 µM浓度下，F1抑制了小鼠腹腔巨噬细胞中LPS诱导的IκB激酶α（IKKα）和IKKβ的磷酸化以及NF-κB（p65）的核内转移。在体内，F1（5 mg/kg）降低了LPS诱导的脓毒症小鼠模型中IL-6、TNF-α和IL-1β的血清水平，并增加了生存率。

Depemokimab (GSK-3511294) 是一种长效的抗IL-15单克隆抗体。Depemokimab 可用于哮喘研究。

Anti-inflammatory agent 15 (化合物 29) 是有效的抗结核分枝杆菌剂，可用于结核病(TB)的研究。Anti-inflammatory agent 15 抑制 Mtb H37Rv 和 M299生长，MIC50分别为 2.3 和 7.8 μM。Anti-inflammatory agent 15也是一种抗炎剂， 通过抑制 iNOS 的表达来抑制 NO，同时也抑制 TNF-α 和 IL-1β 的产生。

HMGB1-IN-2 (compound 15) 是一种针对高度保守的核蛋白 HMGB1 的抑制剂，其在 RAW264.7 细胞中展现出 NO 抑制活性，IC50 为 20.2 μM。 HMGB1-IN-2 (30 μM) 能够减少 IL-1β、TNF-α、caspase-1 p20 的表达，并抑制 NF-κB p65 的磷酸化作用，显示出抗凋亡特性。在脓毒症急性肾损伤模型的小鼠中，HMGB1-IN-2（15 mg kg；腹腔注射）可有效减轻肾脏伤害。此外，HMGB1-IN-2 对 Huh7 细胞和 A549 细胞的 IC50 分别为 77.0 μM 和 82.0 μM。

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。

β-Carboline-1-carboxylic acid is an alkaloid that has been found in P. quassioides and has diverse biological activities. It reduces LPS-induced increases in MCP-1, TNF-α, IL-6, and IL-1β levels in RAW 264.7 cells when used at a concentration of 15 µg/ml and inhibits the epithelial-to-mesenchymal transition (EMT) induced by TGF-β1 in A549 cells. β-Carboline-1-carboxylic acid induces cytotoxicity in CT26.WT, K562, and SGC-7901 cells (IC50s = 14.96, 22.11, and 19.7 µg/ml, respectively) but not HepG2 or A549 cells (IC50s = 36.41 and 41.51 µg/ml, respectively). It also inhibits cAMP phosphodiesterase with an IC50 value of 96 µM.

Benpyrine is a highly specific and orally active TNF-α inhibitor with a KD value of 82.1 μM. Benpyrine tightly binds to TNF-α and blocks its interaction with TNFR1, with an IC50 value of 0.109 μM. Benpyrine has the potential for TNF-α mediated inflammatory and autoimmune disease research[1]. Benpyrine (5-20 μM; 14 hours; RAW264.7 cells) pretreatment results in a dose-dependent decrease in the phosphorylation of IκBα in RAW264.7 cells (stimulated with 10 ng mL TNF-α or 1 μg mL LPS). Benpyrine abolishes the TNF-α-induced nuclear translocation of NF-κB p65 in RAW264.7 cells[1].Benpyrine only blocks cell death induced by TNF-αWT and Y119A, and increases the cell survival rate up to 80%. Benpyrine does not obviously affect L57A- and Y59L-induced cytotoxicity in L929 cells[1]. Benpyrine (25-50 mg kg; oral gavage; daily; for 2 weeks; Balb c mice) treatment significantly relieves the symptoms of collagen-induced arthritis. Benpyrine dose-dependently decreases the levels of proinflammatory cytokines, such as IFN-γ, IL-1β and IL-6, and increases the concentration of the anti-inflammatory cytokine IL-10[1].Endotoxemia murine model shows that Benpyrine (25 mg kg) could attenuate TNF-α-induced inflammation, thereby reducing liver and lung injury[1]. [1]. Weiguang Sun, et al. Discovery of an Orally Active Small Molecule TNF-α Inhibitor. J Med Chem. 2020 Jul 15.

β-Defensin-4 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts. It induces migration of monocytes in vitro when used at a concentration of 10 nM but does not affect migration of neutrophils and eosinophils. β-Defensin-4 (30 μg/ml) stimulates gene expression and production of IL-6, IL-10, CXCL10, CCL2, MIP-3α, and RANTES by keratinocytes. It also stimulates calcium mobilization, migration, and proliferation of keratinocytes when used at concentrations of 30, 10, and 40 μg/ml, respectively. β-Defensin-4 induces IL-31 production by human peripheral blood-derived mast cells in vitro when used at a concentration of 10 μg/ml and by rat mast cells in vivo following a 500 ng intradermal dose. It also inhibits growth of E. coli, P. aeruginosa, and S. aureus with lethal concentration (LC) values of 5, 12, and 15 μM, respectively, of S. carnosus (MIC = 4.5 μg/ml), and of C. albicans with a minimum fungicidal concentration (MFC) value of 7.5 μM.

LL-37 is a cationic and α-helical antimicrobial peptide expressed in human bone marrow, testis, granulocytes, and gingival epithelium and is upregulated in psoriatic lesions. It inhibits growth of Gram-positive E. coli D21 and Gram-negative B. megatarium in a concentration-dependent manner and LL-37 expression is induced in A549 epithelial cells, alveolar macrophages, neutrophils, and monocyte-derived macrophages following M. tuberculosis infection. LL-37 binds sheep erythrocytes coated with S. minnesota Re-LPS and induces agglutination with a minimal agglutinating concentration (MAC) of 12.1 μg/ml. It is a chemoattractant for, and can induce calcium mobilization in, human monocytes, neutrophils, and T cells that naturally express formyl peptide receptor-like 1 (FPRL1) and FPRL1-transfected HEK293 cells. LL-37 (10-15 μM) pretreatment of dengue virus type 2 (DENV-2) reduces its infectivity as well as levels of viral genomic RNA and NS1 antigen. In vivo, LL-37 inhibits cecal ligation and puncture-induced caspase-1 activation and pyroptosis of peritoneal macrophages, reduces levels of the inflammatory cytokines IL-1β, IL-6, and TNF-α, and improves survival in polybacterial septic mice.

COX-2 15-LOX-IN-3 (compound 5k) 为COX-2 15-LOX的一种双重抑制剂，具有分别为0.075 μM和1.97 μM的IC50值。该化合物能显著抑制LPS诱导的细胞产生促炎细胞因子（IL-6, ROS和NO），表明其具备显著的抗炎活性。

JAK-IN-24 是一种 JAK 抑制剂，在 4 μM 或 1 mM ATP 存在时，IC50分别为 0.534 和 24 nM。JAK-IN-24 还抑制 PBMCIL-15诱导的 STAT5磷酸化，IC50为 86.171 nM。

Isomucronulatol 7-O-glucoside 是一种具有生物活性的异黄酮，分离自黄芪中。