tnf-b

Akt NF-κB JNK-IN-1 (Compound 2i) 是一种 Akt、NF-κB 和 JNK 信号通路抑制剂。Akt NF-κB JNK-IN-1 对一氧化氮的产生表现出抑制作用 (IC50: 3.15 μM)，表现出抗炎效果。

Akt NF-κB MAPK-IN-1（compound 2m）为口服活性NO抑制剂，IC50值为7.70 μM，低毒性。该化合物通过抑制Akt NF-κB与MAPK信号通路实现抗炎效应。

Alethine (β-Alethine) 是一种小分子化合物，具有抗肿瘤活性，可用于治疗肿瘤和感染。 Alethine 诱导的TNFα上调增加T 细胞的细胞毒性。

β-Anhydroicaritin 是从乳香提取的一种天然产物，具有重要的生物学和药理学作用，如抗骨质疏松症，雌激素调节和抗肿瘤特性。它改善牙周组织的降解，抑制糖尿病大鼠 TNF-α 和 MMP-3 的合成和分泌。它抑制细胞内 Ca2+的升高，并显著降低 iNOS 蛋白的表达。

2-Methoxyhydroquinone对MAO-A和MAO-B具有抑制活性，还降低 TNF-α-诱导的CCL2的产生，常作为前体用于合成Hsp90抑制剂Geldanamycin。

6-OAU (GTPL5846) 是 GPR84 的替代激动剂，在 Gqi5 嵌合体存在的情况下，在 HEK293 细胞中激活人 GPR84，在 PI 测定中 EC50 为 105 nM。

Ginsenoside Rh1 (Sanchinoside B2) 是人参的一种主要成分，具有抗炎作用，抑制PPAR-γ，TNF-α，IL-6和IL-1β的表达。

Jolkinolide B 是一种从 Euphorbia fischeriana Steud 的根中分离出来的具有生物活性的二萜。 Jolkinolide B 诱导癌细胞凋亡。 Jolkinolide B 可用于预防和治疗骨溶解的研究。

Ansatrienin A is an ansamycin antibiotic and antifungal agent first isolated from S. collinus and S. rishiriensis. In fetal rat long bones, it is an inhibitor of parathyroid hormone-induced calcium release (IC50 = 64 nM), which is a measure of bone resorption, and pp60c-srcM kinase (IC50 = 100 nM). It also inhibits TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1; IC50 = 570 nM). Early in vitro studies showed that ansatrienin A potentiates the chemotherapeutic action of 5-fluorouracil , cisplatin , bleomycin , mitomycin C , and 6-mercaptopurine. It is an oxidized form of ansatrienin B .

Ansatrienin B is an ansamycin antibiotic and antifungal agent first isolated from S. collinus and S. rishiriensis., In fetal rat long bones, it is an inhibitor of parathyroid hormone-induced calcium release (IC50 = 21 nM), which is a measure of bone resorption, and pp60c-src kinase (IC50 = 50 nM). It is an inhibitor of translation at the protein synthesis stage by specific inhibition of L-leucine incorporation (IC50 = 58 nM in A549 cells). It also inhibits TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1; IC50 = 300 nM). Early in vitro studies showed that ansatrienin B potentiates the chemotherapeutic action of 5-fluorouracil , cisplatin , bleomycin , mitomycin C , and 6-mercaptopurine. Ansatrienin B is a hydroquinone form of ansatrienin A .

Mollugin (Rubimaillin) 是Rubia cordifolia L.中主要的生物活性成分。它能通过 p38-Smad 信号通路增强 BMP-2 的成骨作用。它通过抑制 TNF-α 诱导的 NF-κB 激活起抗癌疗效。

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)

Potent inhibitor of NF-κB activation (IC50 = 85 nM); decreases IκBα phosphorylation. Attenuates LPS-induced nitric oxide production and expression of TNF-α, IL-6 and MCP. Suppresses proliferation of HeLa and HCT116 cells. Anti-inflammatory and antitumor. Hu et al (2007) Regulation of c-Src nonreceptor tyrosine kinase activity by bengamide A through inhibition of methionine aminopeptidases. Chem.Biol. 14 764 PMID:17656313 |Johnson et al (2012) Myxobacteria versus sponge-derived alkaloids: the bengamide family identified as potent immune modulating agents by scrutiny of LC-MS ELSD libraries. Bioorg.Med.Chem. 20 4348 PMID:22705020 |Kinder et al (2001) Synthesis and antitumor activity of ester-modified analogues of bengamide B. J.Med.Chem. 44 3692 PMID:11606134

LEO 39652 is a dual-soft PDE4 inhibitor with IC50s of 1.2 nM, 1.2 nM, 3.0 nM and 3.8 nM for PDE4A, PDE4B, PDE4C and PDE4D, respectively. LEO 39652 also inhibits TNF-α with an IC50 value of 6.0 nM. LEO 39652 is used for topical research of Atopic dermatitis (AD) [1]. LEO 39652 shows unbound in vitro potency when measured as LPS induced TNF-α release in human peripheral blood mononuclear cells (PBMC), incubated in serum free medium. LEO 39652 shows a relatively high binding to human serum albumin[2]. LEO 39652 is inactivated both in blood and liver (dual-soft) while stabled in the skin[1].Pharmacokinetic AnalysisLEO 39652 exhibits total clearance (rats 930, minipigs 200 and monkey 300 mL min kg) and ratio to total AUC (rats 4, minipigs 6 and monkey 6 %) following intravenous administration (rats 0.075, minipigs 0.5 and monkeys 2.0 mg kg)[1]. [1]. Jens Larsen, et al. Discovery and Early Clinical Development of Isobutyl 1-[8-Methoxy-5-(1-oxo-3 H-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5- a]pyridin-2-yl]cyclopropanecarboxylate (LEO 39652), a Novel Dual-Soft PDE4 Inhibitor for Topical Treatment of Atopic Dermatitis. J Med Chem. 2020 Dec 10;63(23):14502-14521.[2]. Stefan Eirefelt

Prim-O-glucosylcimifugin (Cimifugin 7-glucoside) 具有强效的抗炎作用。通过调节 JAK2 STAT3 信号传导可抑制iNOS 和COX-2表达。

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.

Forsythoside B 是传统中药植物独一味叶子中分离的一种苯乙醇苷。它可抑制 TNF-alpha，IL-6，IκB， 调节 NF-κB。它抑制炎症反应，具有抗氧化和神经保护作用。

OSS_128167 (SIRT6-IN-1) 是一种选择性沉默调节蛋白 6 (SIRT6) 抑制剂，对 SIRT6，SIRT1 和 SIRT2 的 IC50分别为 89 μM，1578 μM 和 751 μM。它具有抗 HBV、抗癌、抗炎和抗病毒活性，可抑制 HBV 的转录和复制。

Bruceine B 是一种有效的白细胞-内皮细胞粘附抑制剂，可抑制蛋白质和核酸合成。

URMC-099 是一种具有优异的血脑屏障穿透性的，可口服的混合谱系激酶 3 抑制剂，IC50为14 nM。

E3330 是一种口服有效的选择性 AP 内切核酸酶 1 (APE1; REF-1) 抑制剂，可抑制NF-κB DNA 结合活性。它阻断 TNF-α 诱导的肝癌细胞系中 IL-8 的激活，可以抑制癌细胞的生长和迁移，具有抗癌活性。

NG25 trihydrochloride is a type II kinase inhibitor that inhibits MAP4K2 and TAK1. It also inhibits the Src family kinases Src and LYN and Abl family kinases as well as CSK, FER, and p38α. NG 25 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. NG 25 decreases cell viability of HCT116KRASWT, and to a greater degree of HCT116KRASG13D, colorectal cancer cells in a concentration-dependent manner. It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26KRASG12D mouse orthotopic model of colorectal cancer.

Ruscogenin 是一种重要甾体皂苷元，提取自麦冬。它能够抑制 TXNIP NLRP3炎症体激活和 MAPK 途径，改善脑缺血诱导的血脑屏障功能障碍，具有显著抗血栓、抗炎作用。

Schisandrol B (Besigomsin) 是华中五味子的主要活性成分，具有保肝、抗炎、抗糖尿病和抗氧化的作用。它抑制活性氧的产生，也抑制 P-糖蛋白和CYP3A 的活性。