tnf-α-in-2

TNF-α-IN-2 is a highly potent and orally bioavailable inhibitor of tumor necrosis factor alpha (TNFα), exhibiting an IC50 of 25 nM in the HTRF assay. It exerts its inhibitory effects by inducing conformational changes in the TNFα trimer upon binding, resulting in disrupted signaling when the trimer interacts with TNFR1. TNF-α-IN-2 holds promise as a valuable tool for investigating the pathogenesis of rheumatoid arthritis[1].

TAPI-2 is a broad-spectrum inhibitor of MMP (IC50: 20 μM), tumour necrosis factorα-converting enzyme (TACE) and a disintegrin and metalloproteinase (ADAM).

Cot inhibitor-1 hydrochloride is an inhibitor of tumor progression loci-2 kinase (IC50 = 28 nM) and inhibits the production of TNF-α in human whole blood (IC50 = 5.7 nM).

Cot inhibitor-2 is a cot (Tpl2/MAP3K8) inhibitor (IC50: 1.6 nM) with potency, selectivity and oral activity. cot inhibitor-2 inhibits LPS-stimulated TNF-α production in human whole blood with an IC50 of 0.3 μM.

Polygalasaponin F has anti-neuroinflammatory activity, can inhibit the release of inflammatory cytokines TNF-α and NO induced by lipopolysaccharides (LPS) and reduce the expression of inducible nitric oxide synthases. Polygalasaponin F can significantly i

1. β-Anhydroicaritin exhibits immunosuppressive effect on the mouse macrophages stimulated by LPS. 2. β-Anhydroicaritin phytosomes can inhibit enhanced bone turnover induced by ovariectomy, improve BMD the biomechanical properties of vertebrae, without any stimulation on uterus. 3. β-Anhydroicaritin possesses significant protective effects on the zymosan-induced peritonitis mice, which might be associated with the regulation of Ca(2+); influx in macrophages and iNOS expression.

1. Linarin (Acacetin-7-O-rutinoside) (acacetin-7-O-β-d-rutinoside) shows selective dose dependent inhibitory effect on acetylcholinesterase. 2. Linarin alleviates GalN/LPS-induced liver injury by suppressing TNF-α-mediated apoptotic pathways. 3. Linarin prevents A beta-induced neurotoxicity through the activation of PI3K/Akt, which subsequently inhibits GSK-3b and up-regulates Bcl-2. 4. The piperine significantly enhanced the oral absorption of Linarin in rats by inhibiting P-glycoprotein mediated cellular efflux during the intestinal absorption and likely simultaneously by inhibiting the metabolism of Linarin.

Neochlorogenic acid (trans-5-O-Caffeoylquinic acid) is an antioxidant compound used in the treatment of oxidative stress and related afflictions.

9(Z),11(E)-Conjugated linoleic acid is an isomer of linoleic acid that has been found in beef and milk fat.1It binds to peroxisome proliferator-activated receptor α (PPARα; IC50= 140 nM) and activates the receptor in a reporter assay using COS-1 cells expressing mouse PPARα when used at a concentration of 100 μM.29(Z),11(E)-Conjugated linoleic acid inhibits TNF-α-inducedGLUT4expression and increases insulin-stimulated glucose transport in 3T3-L1 adipocytes.3Dietary administration of 9(Z)11(E)-conjugated linoleic acid reduces serum fasting glucose, insulin, and triglyceride levels and decreases white adipose tissue macrophage infiltration inob/obmice. It also increases body weight gain and body fat in weanling mice.4[Matreya, LLC. Catalog No. 1278] 1.Shultz, T.D., Chew, B.P., Seaman, W.R., et al.Inhibitory effect of conjugated dienoic derivatives of linoleic acid and β-carotene on the in vitro growth of human cancer cellsCancer Lett.63(2)125-133(1992) 2.Moya-Camarena, S.Y., Heuvel, J.P.V., Blanchard, S.G., et al.Conjugated linoleic acid is a potent naturally occurring ligand and activator of PPARαJ. Lipid Res.40(8)1426-1433(1999) 3.Moloney, F., Toomey, S., Noone, E., et al.Antidiabetic effects of cis-9, trans-11-conjugated linoleic acid may be mediated via anti-inflammatory effects in white adipose tissueDiabetes56(3)574-582(2007) 4.Pariza, M.W., Park, Y., and Cook, M.E.The biologically active isomers of conjugated linoleic acidProg. Lipid Res.40(4)283-298(2001)

α-Melanocyte-stimulating hormone (α-MSH) is a 13-amino acid peptide hormone produced by post-translational processing of proopiomelanocortin (POMC) in the pituitary gland, as well as in keratinocytes, astrocytes, monocytes, and gastrointestinal cells.1It is an agonist of melanocortin receptor 3 (MC3R) and MC4R that induces cAMP production in Hepa cells expressing the human receptors (EC50s = 0.16 and 56 nM, respectively).2α-MSH (100 pM) reducesS. aureuscolony formation andC. albicansgerm tube formationin vitro.3It inhibits endotoxin-, ceramide-, TNF-α-, or okadaic acid-induced activation of NF-κB in U937 cells.1α-MSH reduces IL-6- or TNF-α-induced ear edema in mice.4It also prevents the development of adjuvant-induced arthritis in rats and increases survival in a mouse model of septic shock. Increased plasma levels of α-MSH are positively correlated with delayed disease progression and reduced death in patients with HIV.1 1.Catania, A., Airaghi, L., Colombo, G., et al.α-melanocyte-stimulating hormone in normal human physiology and disease statesTrends Endocrinol. Metab.11(8)304-308(2000) 2.Miwa, H., Gantz, I., Konda, Y., et al.Structural determinants of the melanocortin peptides required for activation of melanocortin-3 and melanocortin-4 receptorsJ. Pharmacol. Exp. Ther.273(1)367-372(1995) 3.Cutuli, M., Cristiani, S., Lipton, J.M., et al.Antimicrobial effects of a-MSH peptidesJ. Leukoc. Biol.67(2)233-239(2000) 4.Lipton, J.M., Ceriani, G., Macaluso, A., et al.Antiiinflammatory effect of the neuropeptide a-MSH in acute, chronic, and systemic inflammationAnn. N.Y. Acad. Sci.25(741)137-148(1994)

Certolizumab pegol (Certolizumab) is a recombinant, humanized monoclonal antibody fragment that has been modified with polyethylene glycol (PEG), which selectively targets and neutralizes tumor necrosis factor-alpha (TNF-α). This compound is utilized in the research of rheumatoid arthritis and Crohn's disease [1] [2].

D-Trimannuronic acid is an alginate oligomer that originates from seaweed. It can induce TNF-α secretion by mouse macrophage cell lines, making it valuable in pain and vascular dementia research [1][2][3].

Cimiside E has anti-inflammatory activity, it selectively inhibits TNF-α-induced expression of VCAM-1 at least by upregulation of PPAR-γ, and signals for ERK1/2, PI3K, and PKC are involved in this effect.Cimiside E may be an effective chemopreventive agen

Quin C1 is a selective and potent formylpeptide receptor 2 (FPR2/ALX) agonist with anti-inflammatory activity, inhibits neutrophil and lymphocyte production in BALF, and reduces the expression of TNF-α, IL-1β, KC, and TGF-β1.Quin C1 is used in the study of lung injury.

Rhein-13C4 is intended for use as an internal standard for the quantification of rhein by GC- or LC-MS. Rhein is an anti-inflammatory anthraquinone found in rhubarb and is the bioactive derivative of its prodrug diacerein . At 10 μM, rhein inhibits IL-1β signaling, suppressing signaling through NF-κB, and reduces the expression of the matrix metalloproteases MMP-1 and MMP-13.1 It inhibits IKKβ (IC50 = 11.8 μM), decreasing iNOS and IL-6 expression in LPS-stimulated macrophages but paradoxically increasing TNF-α, IL-1β, and HMBG1 expression.2 Rhein shows efficacy against pancreatic fibrosis, chronic pancreatitis, and hyperglycemia-induced pancreatic β-cell apoptosis.3,4 It also inhibits angiogenesis of breast cancer cells under normoxic and hypoxic conditions.5

5,6-Benzoflavone (β-Naphthoflavone) is an exogenous ligand for the aryl hydrocarbon receptor, which disrupts zinc homeostasis in human hepatocellular carcinoma HepG2 cells. 5,6-Benzoflavone (β-Naphthoflavone) possesses anti-inflammatory and antioxidant activities, inhibits LPS-induced inflammation through the AKT/Nrf-2/HO-1-NF-kappaB signaling axis, inhibits TNF-α-induced ICAM-1 and VCAM-1 expression, which can be used to study neurodegenerative diseases.

O-Demethyl apremilast is an active metabolite of the phosphodiesterase 4 (PDE4) inhibitor apremilast .1It inhibits the activity of PDE4 isolated from U937 cells and LPS-induced TNF-α production in isolated human peripheral blood mononuclear cells (PBMCs; IC50s = 8.3 and 5.6 μM, respectively). O-Demethyl apremilast is also an oxidative degradation product of apremilast.2,3 1.Hoffmann, M., Kumar, G., Schafer, P., et al.Disposition, metabolism and mass balance of [14C]apremilast following oral administrationXenobiotica41(12)1063-1075(2011) 2.Lu, Y., Shen, X., Hang, T., et al.Identification and characterization of process-related substances and degradation products in apremilast: Process optimization and degradation pathway elucidationJ. Pharm. Biomed. Anal.14170-78(2017) 3.Bhole, R.P., Naksakhare, S.R., and Bonde, C.G.A stability indicating HPTLC method for apremilast and identification of degradation products using MS/MSJ. Pharm. Sci. & Res.11(5)1861-1869(2019)

Tpl2 kinase inhibitor is an inhibitor of tumor progression locus 2 (Tpl2; IC50= 0.05 μM).1It is selective for Tpl2 over MEK, p38 MAPK, Src, MK2, and PKC (IC50s = >40, 180, >400, 110, and >400 μM, respectively). Tpl2 kinase inhibitor inhibits LPS-induced TNF-α production in isolated human monocytes and whole blood (IC50s = 0.7 and 8.5 μM, respectively). It enhances differentiation induced by calcitriol in HL-60 and U937 leukemia cells when used at a concentration of 5 μM.2Tpl2 kinase inhibitor (5 μM) inhibits the proliferation of KG-1a leukemia cells.3 1.Garvin, L.K., Green, N., Hu, Y., et al.Inhibition of Tpl2 kinase and TNF-α production with 1,7-naphthyridine-3-carbonitriles: Synthesis and structure-activity relationshipsBioor. Med. Chem. Lett.15(23)5288-5292(2005) 2.Wang, X., and Studzinski, G.P.Expression of MAP3 kinase COT1 is up-regulated by 1,25-dihydroxyvitamin D3 in parallel with activated c-jun during differentiation of human myeloid leukemia cellsJ. Steroid. Biochem. Mol. Biol.121(1-2)395-398(2010) 3.Wang, X., Gocek, E., Novik, V., et al.Inhibition of Cot1/Tlp2 oncogene in AML cells reduces ERK5 activation and up-regulates p27Kip1 concomitant with enhancement of differentiation and cell cycle arrest induced by silibinin and 1,25-dihydroxyvitamin D3Cell Cycle9(22)4542-4551(2010)

Resolvin D2 n-3 DPA (RvD2 n-3 DPA) is a specialized pro-resolving mediator (SPM).1It is formed from docosapentaenoic acid , an intermediate in the conversion of eicosapentaenoic acid to docosahexaenoic acid , in human leukocytes. RvD2 n-3 DPA (1 nM) reduces TNF-α-induced chemotaxis and adhesion of isolated human neutrophils.In vivo, RvD2 n-3 DPA (100 ng/animal; i.v.) reduces peritoneal neutrophil infiltration and exudate levels of IL-6 and chemokine (C-C motif) ligand 2 (CCL2) in a mouse model of zymosan-induced inflammation. 1.Dalli, J., Colas, R.A., and Serhan, C.N.Novel n-3 immunoresolvents: Structures and actionsSci. Rep.31940(2013)

Diprovocim-1 is an agonist of the toll-like receptor 1/2 heterodimer.1It induces TNF-α release in THP-1 cells (EC50= 110 pM), an effect that can be inhibited by anti-TLR1 or anti-TLR2 antibodies. Diprovocim-1 (10 mg/kg) increases the production of ovalbumin-specific IgG1 in wild-type, but notTLR2-/-, mice sensitized to ovalbumin.2It also enhances anti-PD-L1 antibody-induced activation of cytotoxic T lymphocytes, reduction of tumor growth, and increases in survival in a B16/F10 murine melanoma model. 1.Morin, M.D., Wang, Y., Jones, B.T., et al.Diprovocims: A new and exceptionally potent class of toll-like receptor agonistsJ. Am. Chem. Soc.140(43)14440-14454(2018) 2.Wang, Y., Su, L., Morin, M.D., et al.Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti-PD-L1 to eliminate melanoma in miceProc. Natl. Acad. Sci. U.S.A.115(37)E8698-E8706(2018)

Ginsenoside Rg6 can inhibit JK cell proliferation in human lymphocytoma and induce its apoptosis, the mechanism may through mitochondrial dysfunction and an increase of Bax expression and decrease of Bcl-2 expression.

Resveratrol-3-O-sulfate is a metabolite of resveratrol . In U-937 cells stimulated with LPS, resveratrol-3-O-sulfate (1 μM) decreases the expression of IL-1α, IL-1β, and IL-6 by 61.2, 76.6, and 42.2%, respectively, and decreases the release of TNF-α and IL-6 to similar levels as resveratrol. It has antioxidant activity in a Trolox assay, dose-dependently decreases growth of Caco-2 colorectal adenocarcinoma cells when used at concentrations ranging from 10 to 100 μM, and induces apoptosis at concentrations of 25 and 50 μM. Resveratrol-3-O-sulfate also displaces rosiglitazone from the outer mitochondrial protein mitoNEET (IC50 = 3.36 μM for the human protein), indicating that it binds to the thiazolidine-2,4-dione (TZD) binding pocket.

Sirtuins (SIRTs) represent a distinct class of trichostatin A-insensitive lysyl-deacetylases (class III HDACs). Human SIRT1 is the homolog of yeast silent information regulator 2 (Sir2) and has been shown to regulate the activity of the p53 tumor suppressor and inhibit apoptosis. Small molecule activators of SIRT1, such as resveratrol, extend lifespan in yeast and C. elegans in a manner that resembles caloric restriction. CAY10591 has been identified as an activator of the enzyme SIRT1. This compound increases fluorescence by 233% in a SIRT1 activity assay. [Activator activity was defined as the percentage of signal increase relative to signal window in the following formula: 100 x (Sample - Signallow)/(Signalhigh - Signallow)]. CAY10591 suppresses TNF-α in a dose-dependent manner. In THP-1 cells, TNF-α levels decreased from 325 pg/ml (control) to 104 and 53 pg/ml with 20 and 60 µM CAY10591, respectively. This activator also has a significant dose-dependent effect on fat mobilization in differentiated adipocytes, which would indicate the potential of SIRT1 activators for anti-obesity or anti-diabetic purposes.

8-Bromo NAD+ serves as a prodrug for the cyclic ADP-ribose (cADPR) inhibitor, 8-bromo cADPR, undergoing conversion to its active form by the enzyme CD38. At a concentration of 1 mM, it effectively inhibits the rise in intracellular calcium levels and chemotaxis triggered by N-formyl-Met-Leu-Phe (fMLP) in mouse bone marrow-derived neutrophils. Furthermore, when applied at 100 µM, this compound reduces LPS-induced nitrite production and decreases the secretion of TNF-α and IL-2 in mouse primary microglial cells.

NF-κB-IN-2 inhibits canonical NF-κB signaling induced by TNF-α in PC-3 cells.

p38 MAPK inhibitor (IC50 = 0.38 μM). Inhibits the release of IL-1β and TNF-α in a peripheral blood mononuclear cell (PBMC) assay (IC50 values are 0.039 and 0.16 μM respectively). Laufer et al (2003) Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes. J.Med.Chem. 46 3230 PMID:12852754 |Kammerer et al (2007) Pharmacokinetics of ML3403 ({4-[5-(4-fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-(1-phenylethyl)-amine), a 4-pyridinylimidazole-type p38 mitogen-activated protein kinase inhibitor. Drug Metab.Dispos. 35 875 PMID:17344341

Mollugin (Rubimaillin) may be a JAK2 inhibitor and inhibits LPS-induced inflammatory responses by blocking the activation of the JAK-STAT pathway. Mollugin as a candidate for a chemotherapeutic agent in OSCCs via the upregulation of the HO-1 and Nrf2 pathways and the downregulation of NF- κ B. Mollugin may be a novel therapeutic candidate for bone loss-associated disorders including osteoporosis, rheumatoid arthritis, and periodontitis. Also, it has anticancer efficacy, can modulate the HER2 pathway in HER2-overexpressing Y cells with a potential role in the treatment and prevention of human breast and ovarian Y with HER2 overexpression.

1. Schisandrol B (Besigomsin) may exert neuroprotective effects by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-κB and MAPKs signaling pathways. 2. Schisandrol B has anti-inflammatory property, potentially result from the inhibition of COX-2, iNOS, IL-6, TNF-α and NO through the down-regulation of RIP2 and NF-κB activation. 3. Schisandrol B induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway. 4. Schisandrol B significantly inhibits cell proliferation in a dose-dependent manner, due to cell cycle arrest in the G1 phase with the downregulation of cyclin D1 expression and Retinoblastoma (RB) phosphorylation.

1. Monotropein (Monotropeine) has antinociceptive action. 2. Monotropein has anti-apoptosis and anti-catabolic activity in chondrocytes. 3. Monotropein has anti-inflammatory action by inhibition of the expressions of inflammatory mediators via NF-κB inactivation, and support its possible therapeutic role in colitis. 4. Monotrope ininhibit the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) mRNA in LPS-induced RAW 264.7 macrophages.

IKK2-IN-4(IKK2 Inhibitor VI) is a highly potent IKK-2 inhibitor with an IC50 value of 25 nM. IKK2-IN-4 inhibited the production of TNF-α in PBMC induced by LPS.

Lacto-N-neotetraose (LNnT), an endogenous metabolite, inhibits TNF-α-induced IL-8 secretion in immature epithelial cells, exhibits anti-inflammatory activity, and enhances wound closure [1] [2] [4].

Homouridine, an analogue of uridine, functions as an intermediate in the synthesis of MMP-2 inhibitor (compound I, IC50 = 150 μM). Moreover, the derivative of homouridine (compound I) inhibits the interaction of TNF-α with its receptor, TNF-αR1 [1].

Semapimod is an inhibitor of proinflammatory cytokine production, capable of suppressing TNF-α, IL-1β, and IL-6. It hinders TLR4 signaling with an IC50 of approximately 0.3 μM, impedes p38 MAPK, and reduces nitric oxide production in macrophages. This compound shows promise for treating various inflammatory and autoimmune disorders [1] [2] [3].

NCI 126224, a toll-like receptor 4 (TLR4) antagonist, demonstrates selective inhibition of nitric oxide (NO) production in RAW 264.7 macrophages, triggered by the TLR4 agonist LPS (IC50 = 0.31 µM), as opposed to minimal effects on NO production induced by agonists for TLR7/8 (R-848), TLR1/2 (Pam3CSK4), and TLR3 (poly(I:C)). Nevertheless, it also effectively inhibits NO production initiated by the TLR2/6 agonist FSL-1 at an IC50 of 0.6 µM in the same cell line. Moreover, NCI 126224 suppresses LPS-induced NF-κB activity in BV-2 microglial cells and reduces LPS-triggered increases in IL-1β and TNF-α levels in RAW 264.7 macrophages with IC50 values of 5.92, 0.42, and 1.54 µM, respectively.

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)

1. Cucurbitacin IIb is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. 2. Cucurbitacin IIb exhibits its anti-inflammatory activity through modula

DCVC inhibits pathogen-stimulated TNF-α in human extra placental membranes in vitro.Target: TNF-αin vitro: DCVC inhibits pathogen stimulated cytokine release from tissue punch cultures. DCVC (5-50 μM) significantly inhibits LTA-, LPS-, and GBS-stimulated cytokine release from tissue cultures as early as 4 h (P ≤ 0.05). In contrast, TCA (up to 500 μM) does not inhibit LTA-stimulated cytokine release from tissue punches. DCVC effects on LTA-stimulated and LPS-stimulated TNF-α release from tissue punch cultures of extraplacental membranes. DCVC effects on GBS-stimulated release of pro-inflammatory cytokines from extraplacental membranes in transwell cultures. [1]. Boldenow E, et al. The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine but not trichloroacetate inhibits pathogen-stimulated TNF-α in human extraplacental membranes in vitro. Reprod Toxicol. 2015 Apr;52:1-6. [2]. Lash LH, et al. Multigenerational study of chemically induced cytotoxicity and proliferation in cultures of human proximal tubular cells. Int J Mol Sci. 2014 Nov 18;15(11):21348-65. [3]. Yoo HS, et al. Comparative analysis of the relationship between trichloroethylene metabolism and tissue-specific toxicity among inbred mouse strains: kidney effects. J Toxicol Environ Health A. 2015;78(1):32-49.

Cetrelimab (JNJ 63723283; JNJ 3283), a humanized IgG4κ monoclonal antibody (mAb) targeting PD-1, binds to PD-1 (Kd=1.72 nM, HEK293) to prevent its interaction with PD-L1 and PD-L2 (IC50s=111.7 ng/mL and 138.6 ng/mL, respectively). This action stimulates peripheral T cells, elevates the levels of IFN-γ, IL-2, and TNF-α, and consequently inhibits tumor growth in vivo [1].

Necroptosis-IN-3 (Cyclohexanecarboxamide, N-(2-thienylmethyl)-) (Compound 69) is a Necroptosis inhibitor that inhibits TNF-α induced necroptosis. Necroptosis-IN-3 (Compound STX1638) also inhibits 11β-HSD1.

1. Ginsenoside Rk3 and Rh4 could have a role in treating inflammatory diseases. 2. Ginsenoside Rk3 is often used as a major ingredient of the compound preparation for ischemic heart diseases.

1. Negletein (7-O-Methylbaicalein) has anti-inflammatory and immunomodulatory activities via inhibition of TNF-α, iNOS and IL-1β. 2. Negletein as a neuroprotectant enhances the action of nerve growth factor and induces neurite outgrowth in PC12 cells. 3. Negletein shows a comparable redox-active potential, and it (50 μM, 4 h) can activate Nrf2. 4. Negletein shows significant antimicrobial activity. 5. Negletein has anti-hypoxia activity, it can significantly prolong the survival time of hypoxic mice.6. Negletein has anti- Alzheimer's disease activity, it inhibits the iron-dependent formation of ROS and also blocks the iron-induced oligomerization of amyloid beta 42 in vitro. 7. Negletein (IC50: 3.89 +/- 0.39 microM) exhibits potent inhibitory activity against nuclear factor of activated T cells (NFAT) transcription factor.

DPP-4-IN-8 (compound 27) is a potent and selective inhibitor of dipeptidyl peptidase 4 (DPP4), with an inhibition constant (Ki) of 0.96 μM. It inhibits the dipeptidase activity of DPP4 in both Caco-2 and HepG-2 cells and dose-dependently reduces the expression of chemokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) [1].

Cathelicidin-2 (CATH-2) (128-153) is a synthetic antimicrobial peptide derived from amino acids 128-153 of chicken CATH-2, demonstrating activity against pathogens such as E. coli, S. aureus, S. enteritidis, and B. globigii in a dose-dependent manner. At a concentration of 40 µM, it induces hemolysis in chicken erythrocytes without exhibiting cytotoxicity towards human peripheral blood mononuclear cells (PBMCs). Additionally, it stimulates the production of the chemokine CCL2 and suppresses LPS-induced secretion of TNF-α, IL-6, IL-8, and IL-10 in human PBMCs.

Necrostatin 2 is an effective necroptosis inhibitor. Necrostatin 2 is also a RIPK1 inhibitor. EC50 for inhibition of necroptosis in FADD-deficient Jurkat T cells treated with TNF-α is 0.05 μM.

AG126 (Tyrphostin AG126) selectively inhibits the phosphorylation of ERK1 (p44) and ERK2 (p42) at 25-50 μM. It blocks the production of TNF-α in vitro2 and in vivo, attenuating signaling through NF-κB, the induced expression of COX-2 and iNOS, and the inflammatory response in diverse animal models. AG-126 weakly inhibits epidermal GFRK (IC50: 450 μM) and platelet-derived GFRK (IC50 > 100 μM).

1. Ginsenoside Rg5 could be a beneficial agent for the treatment of Alzheimer's disease. 2. Ginsenoside Rg5 suppresses LPS-induced nitric oxide (NO) production and proinflammatory TNF-α secretion. 3. Ginsenoside Rg5 can ameliorate lung inflammation possib

Pd-C-II has anti-inflammation activity, it can inhibit TNF-α production and iNOS protein expression and inhibit COX-2 protein expression in LPS-stimulated RAW 264.7 cells. Pd-C-II inhibits anaphylactic mediator release from purified mast cells induced by

1. Isofraxidin (Phytodolor) protects leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in a p53-independent manner. 2. Isofraxidin has a protective effect against LPS-induced ALI, and the protective effect of Isofraxidin seems to result from the inhibition of COX-2 protein expression in the lung, which regulates the production of PGE2. 3. Isofraxidin possesses significant analgesic and anti-inflammatory activities that may be mediated through the regulation of pro-inflammatory cytokines, TNF-α and the phosphorylation of p38 and ERK1/2.

COX-2-IN-10 is a potent inhibitor of COX-2. COX-2-IN-10 exhibits inhibitory effects on the production of IL-6, TNF-α and IL-1β. COX-2-IN-10 inhibits PGE2 production in a concentration-dependent manner with an IC50 value of 2.54 μM. COX-2-IN-10 inhibits the expression of iNOS and COX-2 at the mRNA and protein levels. COX-2-IN-10 inhibited the expression of iNOS and COX-2 at the mRNA and protein levels.

Taxamairin B is a potent anti-inflammatory compound that inhibits the expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and reduces the production of NO and ROS in LPS-induced RAW264.7 cells. Furthermore, it demonstrates substantial protective effects against LPS-induced acute lung injury in mice [1] [2].