TNF-alpha

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TNF-alpha Products

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Catalog No. Product Name Information Product Use Citations Product Validations
E0130New Apigenin-7-O-glucuronide

Apigenin-7-O-glucuronide (Apigenin-7-glucuronide) is the major flavonoid found in milk thistle. Apigenin 7-o-glucuronide inhibits tumor necrosis factor alpha (TNF-α) and total nitrite release in lipopolysaccharide-activated macrophages.

E0314New JTE-607 Dihydrochloride

JTE-607 Dihydrochloride is a prodrug compound that is converted to an active form by ester hydrolysis. JTE-607 is a multiple cytokine production inhibitor that targets CPSF3 and inhibits pre-mRNA processing. JTE-607 inhibits tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8 and IL-10, from LPS-stimulated human PBMCs, with IC50 values of 11 nM, 5.9 nM, 8.8 nM, 7.3 nM and 9.1 nM, respectively.

S0139 MD2-TLR4-IN-1 MD2-TLR4-IN-1 (Compound 22m) is a potent inhibitor of myeloid differentiation protein 2/toll-like receptor 4 (MD2-TLR4). MD2-TLR4-IN-1 (compound 22m) inhibits lipopolysaccharide (LPS)-induced expression of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in macrophages with IC50 of 0.89 μM and 0.53 μM, respectively.
S0752 AUDA AUDA (compound 43) is a potent inhibitor of soluble epoxide hydrolase (sEH) with IC50 of 18 nM and 69 nM for the mouse sEH and human sEH, respectively. AUDA has anti-inflammatory activity that reduces the protein expression of MMP-9, IL-1β, TNF-α and TGF-β. AUDA downregulates Smad3 and p38 signaling pathways.
S0777 Isuzinaxib (APX-115 free base) Isuzinaxib (APX-115 free base, Ewha-18278 free base) is a potent, orally active inhibitor of pan NADPH oxidase (pan-Nox) with Ki of 1.08 μM, 0.57 μM, and 0.63 μM for Nox1, Nox2 and Nox4, respectively. APX-115 free base (Ewha-18278 free base) significantly suppresses the expression of inflammatory molecules including MCP-1/CCL2, IL-6, and TNFα in the diabetic kidney.
S0781 IQ 3 IQ 3 is a specific c-Jun N-terminal kinase (JNK) inhibitor with Kd of 66 nM, 240 nM and 290 nM for JNK3, JNK1 and JNK2, respectively. IQ 3 inhibits LPS-induced NF-κB/AP1 transcriptional activity in THP1-Blue cells with IC50 of 1.4 μM. IQ 3 also inhibits TNF-α and IL-6 production in vitro.
S0787 3-Deazaadenosine hydrochloride 3-Deazaadenosine HCl (3-DZA, c3Ado) is a potent inhibitor of S-adenosylhomocysteine hydrolase with Ki of 3.9 µM. 3-Deazaadenosine HCl inhibits bacterial lipopolysaccharide-induced transcription of TNF-α and IL-1β. 3-Deazaadenosine HCl inhibits the transcriptional activity of NF-κB, prevents FCS-induced Ras carboxyl methylation and reduces FCS-induced ERK1/2 and Akt phosphorylation. 3-Deazaadenosine HCl has anti-inflammatory, anti-proliferative and anti-HIV activities.
Free Radic Biol Med, 2021, 168:25-43
S0949 Cucurbitacin IIb Cucurbitacin IIb (CuIIb, Dihydrocucurbitacin F, 25-deacetyl hemslecin A) inhibits phosphorylation of STAT3, JNK and Erk1/2, enhances the phosphorylation of IκB and NF-κB, blocks nuclear translocation of NF-κB and decreases mRNA levels of IκBα and TNF-α. Cucurbitacin IIb exhibits anti-inflammatory activity and induces apoptosis. Cucurbitacin IIb is isolated from Hemsleya amabilis.
S1029 Lenalidomide (CC-5013) Lenalidomide (CC-5013) is a TNF-α secretion inhibitor with IC50 of 13 nM in PBMCs. Lenalidomide (CC-5013) is a ligand of ubiquitin E3 ligase cereblon (CRBN), and it causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. Lenalidomide promotes cleaved caspase-3 expression and inhibit VEGF expression and induces apoptosis.
Adv Sci (Weinh), 2021, e2004846
Sci Adv, 2021, 7(6)eabd6263
Sci Adv, 2021, 7(23)eabg2697
S1189 Aprepitant (MK-0869) Aprepitant (MK-0869, L-754030) is a potent and selective neurokinin-1 receptor antagonist with IC50 of 0.1 nM. Aprepitant reduces levels of pro-inflammatory cytokines including G-CSF, IL-6, IL-8 and TNFα. Aprepitant inhibits HIV infection of human macrophages.
Cancers (Basel), 2021, 13(15)3871
Phytomedicine, 2021, 95:153864
Nat Commun, 2020, 29;11(1):2673
S1193 Thalidomide (K17) Thalidomide (K17) was introduced as a sedative drug, immunomodulatory agent and also is investigated for treating symptoms of many cancers. Thalidomide inhibits an E3 ubiquitin ligase, which is a CRBN-DDB1-Cul4A complex.
Hum Cell, 2021, 10.1007/s13577-021-00639-4
Hum Cell, 2021, 10.1007/s13577-021-00579-z
Methods Mol Biol, 2021, 2365:3-20
S1273 Amarogentin

Amarogentin (AG), a secoiridoid glycoside mainly extracted from Swertia and Gentiana roots, exhibits anti-oxidative, anti-tumour, and anti-diabetic activities. Amarogentin is an agonist for the bitter taste receptor TAS2R1 and inhibits in LAD-2 cells substance P-induced production of newly synthesized TNF-α. Amarogentin induces apoptosis in human gastric cancer cells (SNU-16) through G2/M cell cycle arrest and PI3K/Akt signalling pathway. Amarogentin (AG) interacts with the α2 subunit of AMP-activated protein kinase (AMPK) and activates the trimeric kinase with EC50 of 277 pM.

S1567 Pomalidomide (CC-4047) Pomalidomide (CC-4047) inhibits LPS-induced TNF-α release with IC50 of 13 nM in PBMCs. Pomalidomide can be utilized in PROTAC as a ligand for targeting E3 ligase and inhibiting the E3 ligase protein cereblon (CRBN). Pomalidomide promotes apoptosis and cell cycle arrest.
Nat Cell Biol, 2021, 10.1038/s41556-021-00766-y
Mol Cell, 2021, 81(6):1170-1186.e10
Sci Adv, 2021, 7(6)eabd6263
S1623 Acetylcysteine (N-acetylcysteine) Acetylcysteine (N-acetyl-l-cysteine, NAC) is a ROS(reactive oxygen species) inhibitor that antagonizes the activity of proteasome inhibitors. It is also a tumor necrosis factor production inhibitor. Acetylcysteine(N-acetyl-l-cysteine) suppresses TNF-induced NF-κB activation through inhibition of IκB kinases. Acetylcysteine(N-acetyl-l-cysteine) induces apoptosis via the mitochondria-dependent pathway. Acetylcysteine(N-acetyl-l-cysteine) inhibits ferroptosis and virus replication.Solutions of Acetylcysteine are best fresh-prepared.
J Clin Invest, 2021, e152067
EMBO Mol Med, 2021, 13(9):e13193
Elife, 2021, 10e69795
S1833 Butoconazole nitrate Butoconazole nitrate (RS-35887) is an anti-fungal agent that inhibits PHA-stimulated release of cytokines-- IL-2, TNFα, IFN and GM-CSF from human peripheral blood lymphocytes (IC50 of 7.2 μg/mL, 14.4 μg/mL, 7.36 μg/mL and 7.6 μg/mL, respectively).
S2465 CPI-1189 CPI-1189 (REN 1654, REN 1189) is the proapoptotic cytokine tumor necrosis factor (TNF) alpha inhibitor. CPI-1189 intracellularly inhibits the p38 mitogen-activated protein kinase phosphoactivation and shows neuroprotective effects.
Aging (Albany NY), 2021, 13(5):6712-6723
S3138 Methylthiouracil Methylthiouracil (NSC-193526, NSC-9378) is an antithyroid agent. Methylthiouracil suppresses the production TNF-α and IL-6, and the activation of NF-κB and ERK1/2.
S3231New UCB-9260 UCB-9260 is an orally active inhibitor that inhibits TNF signalling by stabilising an asymmetric form of the trimer. UCB-9260 binds TNF with Kd of 13  nM. UCB-9260 also inhibits NF-κB with IC50 of 202 nM after TNF stimulation.
S3236 Mesaconitine Mesaconitine, one of the aconite alkaloids in Aconiti tuber, increases the [Ca2+]i level in endothelial cells by influx of Ca2+ from extracellular spaces.
S3261 Myrislignan Myrislignan, a lignan isolated from Myristica fragrans Houtt, possesses anti-inflammatory activities. Myrislignan inhibits interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). Myrislignan significantly inhibits the expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) dose-dependently in LPS-stimulated macrophage cells. Myrislignan inhibits the NF-κB signalling pathway activation.
S3292 Falcarindiol Falcarindiol (FAD, (3R,8S)-Falcarindiol, FaDOH) is a natural polyacetylene compound found rich in many plants of the Umbelliferae family. Falcarindiol suppresses LPS-stimulated expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). Falcarindiol attenuates the LPS-induced activation of JNK, ERK, STAT1, and STAT3 signaling molecules.
Front Pharmacol, 2021, 12:656697
S3293 Gardenoside Gardenoside is a natural compound extracted from Gardenia fruits, with hepatoprotective properties. Gardenoside inhibits TNF-α, IL-1β, IL-6 and NFκB activation. Gardenoside also has an inhibitory effect on free fatty acids (FFA)-induced cellular steatosis. Gardenoside suppresses the pain in rats model of chronic constriction injury by regulating the P2X3 and P2X7 receptors.
S3299 Demethyleneberberine Demethyleneberberine (DMB), a component of Cortex Phellodendri Chinensis (CPC), significantly alleviates the weight loss and diminishes myeloperoxidase (MPO) activity, while significantly reduces the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and inhibits the activation of NF-κB signaling pathway. Demethyleneberberine (DMB) potentially ameliorates NAFLD (Non-alcoholic fatty liver disease) by activating AMPK pathways.
S3304 Stylopine Stylopine ((R,S)-Stylopine, Tetrahydrocoptisine) reduces nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. Stylopine is a major component of the leaf of Chelidonium majus L.
S3515New Benpyrine racemate Benpyrine racemate ((Rac)-Benpyrine) is a potent, highly specific and orally active inhibitor of TNF-α and attenuates TNF-α-induced inflammation, thereby reducing liver and lung injury.
S3871 Muscone Muscone (3-Methylcyclopentadecanone, Methylexaltone), a flavouring ingredient, is an organic compound that is the primary contributor to the odor of musk and also a potent anti-inflammatory agent. Muscone significantly downregulats the levels of LPS-induced inflammatory cytokines and inhibits NF-κB and NLRP3 inflammasome activation in BMDMs. Muscone remarkably decreases the levels of inflammatory cytokines (IL-1β, TNF-α and IL-6).
J Pharm Pharmacol, 2019, 71(11):1706-1713
S3924 Ginsenoside Rb1 Ginsenoside Rb1 (Gypenoside Ⅲ) is a protopanaxadiol that has diverse in vitro and in vivo effects, including neuroprotective, anti-inflammatory, and anti-obesity actions. Ginsenoside Rb1, a main constituent of the root of Panax ginseng, inhibits Na+, K+-ATPase activity with IC50 of 6.3±1.0 μM. Ginsenoside also inhibits IRAK-1 activation and phosphorylation of NF-κB p65. Ginsenoside Rb1 reduces the expressions of TLR3, TLR4 and TRAF-6, and down-regulates the levels of TNF-α, IFN-β and iNOS.
J Biol Chem, 2021, S0021-9258(21)00790-0
Mol Immunol, 2021, 139:140-152
J Ethnopharmacol, 2021, S0378-8741(21)00169-0
S4238 Cepharanthine Cepharanthine (NSC-623442) is a biscoclaurine alkaloid inhibiting tumor necrosis factor (TNF)-α-mediated NFκB stimulation, plasma membrane lipid peroxidation and platelet aggregation and suppressing cytokine production.
Biochem Biophys Res Commun, 2019, 517(3):407-412
Front Pharmacol, 2018, 9:210
S4902 QNZ (EVP4593) QNZ (EVP4593) shows potent inhibitory activity toward both NF-κB activation and TNF-α production with IC50 of 11 nM and 7 nM in Jurkat T cells, respectively.
Biomed Pharmacother, 2022, 145:112437
Int Immunopharmacol, 2022, 102:108380
Nat Commun, 2021, 12(1):2788
S6727 AX-024 HCl AX-024 HCl blocks the interaction of the CD3ε PRS with SH3.1(Nck). AX-024 HCl also inhibits IL-6, TNF-α, IFN-γ, IL-10 and IL-17A.
S6850 NE 52-QQ57 NE 52-QQ57 is a selective, and orally available antagonist of G-protein coupled receptor 4 (GPR4) with IC50 of 0.07 μM. NE 52-QQ57 effectively blocks GPR4-mediated cAMP accumulation with IC50 of 26.8 nM in HEK293 cells. The antagonism of GPR4 with NE 52-QQ57 significantly inhibits the AGE-induced increased expression of several key inflammatory cytokines and signaling molecules, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase 2 (COX2), and prostaglandin E2 (PGE2).
S7455 Resatorvid (TAK-242) Resatorvid (TAK-242, CLI-095) is a small-molecule-specific inhibitor of Toll-like receptor (TLR) 4 signaling, blocking LPS-induced production of NO, TNF-α and IL-6 in macrophages with IC50 of 1.8 nM, 1.9 nM and 1.3 nM, respectively. Resatorvid downregulates expression of TLR4 downstream signaling molecules MyD88 and TRIF. Resatorvid inhibits autophagy.
FASEB J, 2021, 35(4):e21485
Int J Biol Macromol, 2021, 183:145-157
Front Pharmacol, 2021, 12:626949
S8034 Apremilast (CC-10004) Apremilast (CC-10004) is a potent and orally active PDE4 and TNF-α inhibitor with IC50 of 74 nM and 77 nM, respectively.
Int J Mol Sci, 2021, 22(23)12878
J Immunotoxicol, 2021, 18(1):154-162
Acta Pharmaceutica Sinica B, 2021, 10.1016/j.apsb.2021.04.007
S8037 Necrostatin-1 Necrostatin-1 (Nec-1) is a specific RIP1 (RIPK1) inhibitor and inhibits TNF-α-induced necroptosis with EC50 of 490 nM in 293T cells. Necrostatin-1 also blocks IDO and suppresses autophagy and apoptosis.
Int J Mol Sci, 2022, 23(1)506
Cell, 2021, S0092-8674(21)00885-0
Nat Immunol, 2021, 22(9):1107-1117
S8224New PF-3644022

PF-3644022 is a potent freely reversible ATP-competitive inhibitor of MAPKAPK2 (MK2) with an Ki of 3 nM. PF-3644022 also potently inhibits TNFα production with an IC50 of 160 nM.

S8261 GSK583 GSK583 is a highly potent and selective inhibitor of RIP2 kinase with IC50 of 5 nM. GSK583 also inhibits both TNF-α and IL-6 production with IC50 of ~200 nM in explant cultures.
Cancer Res, 2020, canres.530.2020
J Neuroinflammation, 2020, 17(1):364
S8279 Shikonin (C.I. 75535) Shikonin (C.I. 75535, Anchusin, Anchusa acid, Alkanna Red, Isoarnebin 4, NSC 252844), a potent and specific Pyruvate kinase M2 (PKM2) inhibitor, is a major component of zicao (purple gromwell, the dried root of Lithospermum erythrorhizon), a Chinese herbal medicine with various biological activities. It is also an inhibitor of TMEM16A chloride channel activity using cell-based fluorescent-quenching assay. Shikonin exerts an anti-inflammatory effect by inhibiting tumor necrosis factor-α (TNF-α) and prevents activation of nuclear factor-κB (NF-κB) pathway via proteasome inhibition.
J Cancer, 2021, 12(1):76-88
Cancer Sci, 2021, 112(9):3507-3519
J Cell Mol Med, 2021, 10.1111/jcmm.17007
S8484 GSK2982772 GSK2982772 is an ATP competitive receptor-interacting protein-1 (RIP1) kinase (RIPK1) inhibitor with the IC50 value of 16 nM. It has exquisite kinase specificity and excellent activity in blocking many TNF-dependent cellular responses.
Antioxidants (Basel), 2021, 10(9)1347
Mol Cell Biochem, 2021, 10.1007/s11010-021-04136-y
Exp Ther Med, 2021, 21(2):163
S9075 Mulberroside A Mulberroside A, isolated from the ethanol extract of Morus alba roots, is widely employed as an active ingredient in cosmetic products due to its anti-tyrosinase and anti-oxidant activities. Mulberroside A decreases the expressions of TNF-α, IL-1β and IL-6 and inhibits the activation of NALP3, caspase-1 and NF-κB and the phosphorylation of ERK, JNK and p38.
S9090 Corilagin Corilagin, discovered in many medicinal plants such as Phyllanthus speices etc., has multiple activities including anti-oxidative, anti-inflammatory, anti-apoptotic, hepatoprotective and others. It is an inhibitor of TNF-α.
S9129 20(S)-Ginsenoside Rh1 20(S)-Ginsenoside Rh1 (Prosapogenin A2, Sanchinoside B2, Sanchinoside Rh1) is one of major bioactive compounds extracted from red ginseng, which has been increasingly used for enhancing cognition and physical health worldwide. It exhibits potent characteristics of anti-inflammatory, antioxidant, immunomodulatory effects, and positive effects on the nervous system. Ginsenoside Rh1 inhibits the expression of PPAR-γ, TNF-α, IL-6, and IL-1β.
S9184 Forsythoside B Forsythoside B is a phenylethanoid glycoside isolated from the leaves of Lamiophlomis rotata Kudo, a Chinese folk medicinal plant. Forsythoside B has potent neuroprotective effects and has anti-inflammation, antioxidant, and antisepsis properties. Forsythoside B could inhibit TNF-alpha, IL-6, IκB and modulate NF-κB.
S9374 2',5'-Dihydroxyacetophenone 2',5'-Dihydroxyacetophenone (DHAP, 2-Acetylhydroquinone, Quinacetophenone) is a mixture of dihydroxyacetophenone isomers is used in food flavouring. 2',5'-Dihydroxyacetophenone significantly inhibits NO production via the suppression of iNOS expression. 2',5'-Dihydroxyacetophenone significantly decreases levels of the pro-inflammatory cytokines TNF-α and IL-6 by blocking the ERK1/2 and NF-κB signaling pathways.
Pathol Oncol Res, 2019, 25(1):301-309
S9396 Geraniin Geraniin, a hydrolysable polyphenol derived from Nephelium lappaceum L. fruit rind, has been shown to possess significant antioxidant activity in vitro.The IC50 values of TNF-α release inhibition were 43 μM for geraniin.
S9417 Homoplantaginin Homoplantaginin (Hispidulin-7-glucoside), a main flavonoid from a traditional Chinese medicine Salvia plebeia, has anti-inflammatory and anti-oxidant properties. Homoplantaginin inhibits TNF-α and IL-6 mRNA expression, IKKβ and NF-κB phosphorylation.
S9502 Madecassic acid Madecassic acid (Brahmic acid), a natural triterpene first isolated from C. asiatica, has diverse anti-inflammatory and anti-diabetic effects, blocking NF-κB activation in macrophages and causing by iNOS, COX-2, TNF-alpha, IL-1beta and IL-6 inhibition.
A2010 Adalimumab (anti-TNF-alpha) Adalimumab (anti-TNF-alpha) is the first fully human, recombinant IgG1 monoclonal antibody that specifically targets human TNF-alpha, MW: 144.19 KD.
Toxicol In Vitro, 2021, 73:105134
Nature, 2020, 584(7822):608-613
Nature, 2020, 584(7822):608-613
A5046 TNF Receptor II Rabbit Recombinant mAb

TNF Receptor II Antibody detects endogenous levels of total TNF Receptor II.

S2979 CU-T12-9 CU-T12-9 is a specific agonist of Toll-like receptor (TLR) 1/2 with EC50 of 52.9 nM in HEK-Blue hTLR2 SEAP assay. CU-T12-9 activates both the innate and the adaptive immune systems. CU-T12-9 signals through NF-κB and invokes an elevation of the downstream effectors TNF-α, IL-10, and iNOS.
S3865 Taurochenodeoxycholic acid Taurochenodeoxycholic acid (Taurochenodeoxycholate, TCDCA, Chenodeoxycholyltaurine), a bile acid formed in the liver of most species, is used as a cholagogue and choleretic.
Nat Commun, 2021, 12(1):6479
Microbiome, 2019, 7(1):145
S5584 Citronellol Citronellol (Dihydrogeraniol, (±)-β-Citronellol), a constituent of rose and geranium oils, is used in perfumes and insect repellents. Citronellol can cause necrotic apoptosis of NCI-H1299 cells by up-regulating TNF-α, RIP1 / RIP3 activities, and down-regulating caspase-3 / caspase-8 activities. Citronellol also results in a biphasic increase in ROS production at 1 h and at 12 h in NCI-H1299 cells.
S7963 TIC10 (ONC201) TIC10 (ONC201) inactivates Akt and ERK to induce TNF-related apoptosis-inducing ligand (TRAIL) through Foxo3a, possesses superior drug properties: delivery across the blood-brain barrier, superior stability and improved pharmacokinetics. Phase 1/2.
Mol Cell, 2020, 80(6):1104-1122.e9
ACS Chem Biol, 2019, 14(5):1020-1029
Eur J Pharmacol, 2019, 857:172423
S5851 4'-Methoxychalcone 4'-Methoxychalcone, found in citrus, is chalcone derivative that has shown diverse pharmacological properties, including anti-tumor and anti-inflammatory activities. 4'-Methoxychalcone significantly enhanced adipocyte differentiation, in part, by its potent effects on PPARγ activation and by its reverse effect on TNF-α.
S6643 R-7050 R-7050 is a cell permeable TNF-α receptor antagonist and is 2.3-fold more selective for TNF-α-mediated signaling than for that driven by IL-1β.
Research Square, 2021, 10.21203/rs.3.rs-611538/v1
Cancer Sci, 2020, 112(1):168-177
Cell Signal, 2020, 73:109702
S6347New 5'-N-Ethylcarboxamidoadenosine (NECA) 5'-N-Ethylcarboxamidoadenosine (NECA, 5'-(N-Ethylcarboxamido)adenosine, Adenosine-5'N-ethylcarboxamide, 5'-Ethylcarboxamidoadenosine) is a stable, nonselective adenosine receptor agonist. 5'-N-Ethylcarboxamidoadenosine acts via multiple mechanisms including: reducing diabetes-induced oxidative stress, inhibiting gene expression of IL-18, TNF-α and ICAM-1 (intercellular adhesion molecule 1 (CD54)), and blocking activation of the JNK-MAPK pathway.
S7942 Bioymifi Bioymifi, a small-molecule death receptor 5 (DR5) agonist, binds to the extracellular domain(ECD) of DR5 with a Kd of 1.2 μM but showed little binding affinity to the DR4 ECD. It induces DR5 clustering and aggregation, leading to apoptosis.
Front Immunol, 2020, 11:1345
S8133 Resiquimod (R-848) Resiquimod (R-848, S28463) is an immune response modifier that acts as a potent TLR 7/TLR 8 agonist that induces the upregulation of cytokines such as TNF-α, IL-6 and IFN-α. Resiquimod reduces hepatitis C virus (HCV) infection. Phase 2.
Pharmaceutics, 2021, 13(3)365
bioRxiv, 2021, 2021.03.31.437792
Vaccines (Basel), 2020, 15;8(2):E186
S1537 Vadimezan (ASA404) Vadimezan (ASA404, NSC 640488, DMXAA) is a vascular disrupting agents (VDA) and competitive inhibitor of DT-diaphorase with Ki of 20 μM and IC50 of 62.5 μM in cell-free assays, respectively. DMXAA (Vadimezan) is also a STING agonist with potential antineoplastic activity. DMXAA (Vadimezan) potently induces IFN-β but relatively low TNF-α expression in vitro. DMXAA (Vadimezan) has antiviral activity. Phase 3.
Cell, 2022, 185(1):169-183.e19
Yonsei Med J, 2022, 63(1):42-55
J Clin Invest, 2021, e144339
E0130New Apigenin-7-O-glucuronide

Apigenin-7-O-glucuronide (Apigenin-7-glucuronide) is the major flavonoid found in milk thistle. Apigenin 7-o-glucuronide inhibits tumor necrosis factor alpha (TNF-α) and total nitrite release in lipopolysaccharide-activated macrophages.

E0314New JTE-607 Dihydrochloride

JTE-607 Dihydrochloride is a prodrug compound that is converted to an active form by ester hydrolysis. JTE-607 is a multiple cytokine production inhibitor that targets CPSF3 and inhibits pre-mRNA processing. JTE-607 inhibits tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8 and IL-10, from LPS-stimulated human PBMCs, with IC50 values of 11 nM, 5.9 nM, 8.8 nM, 7.3 nM and 9.1 nM, respectively.

S0139 MD2-TLR4-IN-1 MD2-TLR4-IN-1 (Compound 22m) is a potent inhibitor of myeloid differentiation protein 2/toll-like receptor 4 (MD2-TLR4). MD2-TLR4-IN-1 (compound 22m) inhibits lipopolysaccharide (LPS)-induced expression of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in macrophages with IC50 of 0.89 μM and 0.53 μM, respectively.
S0752 AUDA AUDA (compound 43) is a potent inhibitor of soluble epoxide hydrolase (sEH) with IC50 of 18 nM and 69 nM for the mouse sEH and human sEH, respectively. AUDA has anti-inflammatory activity that reduces the protein expression of MMP-9, IL-1β, TNF-α and TGF-β. AUDA downregulates Smad3 and p38 signaling pathways.
S0777 Isuzinaxib (APX-115 free base) Isuzinaxib (APX-115 free base, Ewha-18278 free base) is a potent, orally active inhibitor of pan NADPH oxidase (pan-Nox) with Ki of 1.08 μM, 0.57 μM, and 0.63 μM for Nox1, Nox2 and Nox4, respectively. APX-115 free base (Ewha-18278 free base) significantly suppresses the expression of inflammatory molecules including MCP-1/CCL2, IL-6, and TNFα in the diabetic kidney.
S0781 IQ 3 IQ 3 is a specific c-Jun N-terminal kinase (JNK) inhibitor with Kd of 66 nM, 240 nM and 290 nM for JNK3, JNK1 and JNK2, respectively. IQ 3 inhibits LPS-induced NF-κB/AP1 transcriptional activity in THP1-Blue cells with IC50 of 1.4 μM. IQ 3 also inhibits TNF-α and IL-6 production in vitro.
S0787 3-Deazaadenosine hydrochloride 3-Deazaadenosine HCl (3-DZA, c3Ado) is a potent inhibitor of S-adenosylhomocysteine hydrolase with Ki of 3.9 µM. 3-Deazaadenosine HCl inhibits bacterial lipopolysaccharide-induced transcription of TNF-α and IL-1β. 3-Deazaadenosine HCl inhibits the transcriptional activity of NF-κB, prevents FCS-induced Ras carboxyl methylation and reduces FCS-induced ERK1/2 and Akt phosphorylation. 3-Deazaadenosine HCl has anti-inflammatory, anti-proliferative and anti-HIV activities.
Free Radic Biol Med, 2021, 168:25-43
S0949 Cucurbitacin IIb Cucurbitacin IIb (CuIIb, Dihydrocucurbitacin F, 25-deacetyl hemslecin A) inhibits phosphorylation of STAT3, JNK and Erk1/2, enhances the phosphorylation of IκB and NF-κB, blocks nuclear translocation of NF-κB and decreases mRNA levels of IκBα and TNF-α. Cucurbitacin IIb exhibits anti-inflammatory activity and induces apoptosis. Cucurbitacin IIb is isolated from Hemsleya amabilis.
S1029 Lenalidomide (CC-5013) Lenalidomide (CC-5013) is a TNF-α secretion inhibitor with IC50 of 13 nM in PBMCs. Lenalidomide (CC-5013) is a ligand of ubiquitin E3 ligase cereblon (CRBN), and it causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. Lenalidomide promotes cleaved caspase-3 expression and inhibit VEGF expression and induces apoptosis.
Adv Sci (Weinh), 2021, e2004846
Sci Adv, 2021, 7(6)eabd6263
Sci Adv, 2021, 7(23)eabg2697
S1189 Aprepitant (MK-0869) Aprepitant (MK-0869, L-754030) is a potent and selective neurokinin-1 receptor antagonist with IC50 of 0.1 nM. Aprepitant reduces levels of pro-inflammatory cytokines including G-CSF, IL-6, IL-8 and TNFα. Aprepitant inhibits HIV infection of human macrophages.
Cancers (Basel), 2021, 13(15)3871
Phytomedicine, 2021, 95:153864
Nat Commun, 2020, 29;11(1):2673
S1193 Thalidomide (K17) Thalidomide (K17) was introduced as a sedative drug, immunomodulatory agent and also is investigated for treating symptoms of many cancers. Thalidomide inhibits an E3 ubiquitin ligase, which is a CRBN-DDB1-Cul4A complex.
Hum Cell, 2021, 10.1007/s13577-021-00639-4
Hum Cell, 2021, 10.1007/s13577-021-00579-z
Methods Mol Biol, 2021, 2365:3-20
S1273 Amarogentin

Amarogentin (AG), a secoiridoid glycoside mainly extracted from Swertia and Gentiana roots, exhibits anti-oxidative, anti-tumour, and anti-diabetic activities. Amarogentin is an agonist for the bitter taste receptor TAS2R1 and inhibits in LAD-2 cells substance P-induced production of newly synthesized TNF-α. Amarogentin induces apoptosis in human gastric cancer cells (SNU-16) through G2/M cell cycle arrest and PI3K/Akt signalling pathway. Amarogentin (AG) interacts with the α2 subunit of AMP-activated protein kinase (AMPK) and activates the trimeric kinase with EC50 of 277 pM.

S1567 Pomalidomide (CC-4047) Pomalidomide (CC-4047) inhibits LPS-induced TNF-α release with IC50 of 13 nM in PBMCs. Pomalidomide can be utilized in PROTAC as a ligand for targeting E3 ligase and inhibiting the E3 ligase protein cereblon (CRBN). Pomalidomide promotes apoptosis and cell cycle arrest.
Nat Cell Biol, 2021, 10.1038/s41556-021-00766-y
Mol Cell, 2021, 81(6):1170-1186.e10
Sci Adv, 2021, 7(6)eabd6263
S1623 Acetylcysteine (N-acetylcysteine) Acetylcysteine (N-acetyl-l-cysteine, NAC) is a ROS(reactive oxygen species) inhibitor that antagonizes the activity of proteasome inhibitors. It is also a tumor necrosis factor production inhibitor. Acetylcysteine(N-acetyl-l-cysteine) suppresses TNF-induced NF-κB activation through inhibition of IκB kinases. Acetylcysteine(N-acetyl-l-cysteine) induces apoptosis via the mitochondria-dependent pathway. Acetylcysteine(N-acetyl-l-cysteine) inhibits ferroptosis and virus replication.Solutions of Acetylcysteine are best fresh-prepared.
J Clin Invest, 2021, e152067
EMBO Mol Med, 2021, 13(9):e13193
Elife, 2021, 10e69795
S1833 Butoconazole nitrate Butoconazole nitrate (RS-35887) is an anti-fungal agent that inhibits PHA-stimulated release of cytokines-- IL-2, TNFα, IFN and GM-CSF from human peripheral blood lymphocytes (IC50 of 7.2 μg/mL, 14.4 μg/mL, 7.36 μg/mL and 7.6 μg/mL, respectively).
S2465 CPI-1189 CPI-1189 (REN 1654, REN 1189) is the proapoptotic cytokine tumor necrosis factor (TNF) alpha inhibitor. CPI-1189 intracellularly inhibits the p38 mitogen-activated protein kinase phosphoactivation and shows neuroprotective effects.
Aging (Albany NY), 2021, 13(5):6712-6723
S3138 Methylthiouracil Methylthiouracil (NSC-193526, NSC-9378) is an antithyroid agent. Methylthiouracil suppresses the production TNF-α and IL-6, and the activation of NF-κB and ERK1/2.
S3231New UCB-9260 UCB-9260 is an orally active inhibitor that inhibits TNF signalling by stabilising an asymmetric form of the trimer. UCB-9260 binds TNF with Kd of 13  nM. UCB-9260 also inhibits NF-κB with IC50 of 202 nM after TNF stimulation.
S3236 Mesaconitine Mesaconitine, one of the aconite alkaloids in Aconiti tuber, increases the [Ca2+]i level in endothelial cells by influx of Ca2+ from extracellular spaces.
S3261 Myrislignan Myrislignan, a lignan isolated from Myristica fragrans Houtt, possesses anti-inflammatory activities. Myrislignan inhibits interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). Myrislignan significantly inhibits the expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) dose-dependently in LPS-stimulated macrophage cells. Myrislignan inhibits the NF-κB signalling pathway activation.
S3292 Falcarindiol Falcarindiol (FAD, (3R,8S)-Falcarindiol, FaDOH) is a natural polyacetylene compound found rich in many plants of the Umbelliferae family. Falcarindiol suppresses LPS-stimulated expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). Falcarindiol attenuates the LPS-induced activation of JNK, ERK, STAT1, and STAT3 signaling molecules.
Front Pharmacol, 2021, 12:656697
S3293 Gardenoside Gardenoside is a natural compound extracted from Gardenia fruits, with hepatoprotective properties. Gardenoside inhibits TNF-α, IL-1β, IL-6 and NFκB activation. Gardenoside also has an inhibitory effect on free fatty acids (FFA)-induced cellular steatosis. Gardenoside suppresses the pain in rats model of chronic constriction injury by regulating the P2X3 and P2X7 receptors.
S3299 Demethyleneberberine Demethyleneberberine (DMB), a component of Cortex Phellodendri Chinensis (CPC), significantly alleviates the weight loss and diminishes myeloperoxidase (MPO) activity, while significantly reduces the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and inhibits the activation of NF-κB signaling pathway. Demethyleneberberine (DMB) potentially ameliorates NAFLD (Non-alcoholic fatty liver disease) by activating AMPK pathways.
S3304 Stylopine Stylopine ((R,S)-Stylopine, Tetrahydrocoptisine) reduces nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. Stylopine is a major component of the leaf of Chelidonium majus L.
S3515New Benpyrine racemate Benpyrine racemate ((Rac)-Benpyrine) is a potent, highly specific and orally active inhibitor of TNF-α and attenuates TNF-α-induced inflammation, thereby reducing liver and lung injury.
S3871 Muscone Muscone (3-Methylcyclopentadecanone, Methylexaltone), a flavouring ingredient, is an organic compound that is the primary contributor to the odor of musk and also a potent anti-inflammatory agent. Muscone significantly downregulats the levels of LPS-induced inflammatory cytokines and inhibits NF-κB and NLRP3 inflammasome activation in BMDMs. Muscone remarkably decreases the levels of inflammatory cytokines (IL-1β, TNF-α and IL-6).
J Pharm Pharmacol, 2019, 71(11):1706-1713
S3924 Ginsenoside Rb1 Ginsenoside Rb1 (Gypenoside Ⅲ) is a protopanaxadiol that has diverse in vitro and in vivo effects, including neuroprotective, anti-inflammatory, and anti-obesity actions. Ginsenoside Rb1, a main constituent of the root of Panax ginseng, inhibits Na+, K+-ATPase activity with IC50 of 6.3±1.0 μM. Ginsenoside also inhibits IRAK-1 activation and phosphorylation of NF-κB p65. Ginsenoside Rb1 reduces the expressions of TLR3, TLR4 and TRAF-6, and down-regulates the levels of TNF-α, IFN-β and iNOS.
J Biol Chem, 2021, S0021-9258(21)00790-0
Mol Immunol, 2021, 139:140-152
J Ethnopharmacol, 2021, S0378-8741(21)00169-0
S4238 Cepharanthine Cepharanthine (NSC-623442) is a biscoclaurine alkaloid inhibiting tumor necrosis factor (TNF)-α-mediated NFκB stimulation, plasma membrane lipid peroxidation and platelet aggregation and suppressing cytokine production.
Biochem Biophys Res Commun, 2019, 517(3):407-412
Front Pharmacol, 2018, 9:210
S4902 QNZ (EVP4593) QNZ (EVP4593) shows potent inhibitory activity toward both NF-κB activation and TNF-α production with IC50 of 11 nM and 7 nM in Jurkat T cells, respectively.
Biomed Pharmacother, 2022, 145:112437
Int Immunopharmacol, 2022, 102:108380
Nat Commun, 2021, 12(1):2788
S6727 AX-024 HCl AX-024 HCl blocks the interaction of the CD3ε PRS with SH3.1(Nck). AX-024 HCl also inhibits IL-6, TNF-α, IFN-γ, IL-10 and IL-17A.
S6850 NE 52-QQ57 NE 52-QQ57 is a selective, and orally available antagonist of G-protein coupled receptor 4 (GPR4) with IC50 of 0.07 μM. NE 52-QQ57 effectively blocks GPR4-mediated cAMP accumulation with IC50 of 26.8 nM in HEK293 cells. The antagonism of GPR4 with NE 52-QQ57 significantly inhibits the AGE-induced increased expression of several key inflammatory cytokines and signaling molecules, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase 2 (COX2), and prostaglandin E2 (PGE2).
S7455 Resatorvid (TAK-242) Resatorvid (TAK-242, CLI-095) is a small-molecule-specific inhibitor of Toll-like receptor (TLR) 4 signaling, blocking LPS-induced production of NO, TNF-α and IL-6 in macrophages with IC50 of 1.8 nM, 1.9 nM and 1.3 nM, respectively. Resatorvid downregulates expression of TLR4 downstream signaling molecules MyD88 and TRIF. Resatorvid inhibits autophagy.
FASEB J, 2021, 35(4):e21485
Int J Biol Macromol, 2021, 183:145-157
Front Pharmacol, 2021, 12:626949
S8034 Apremilast (CC-10004) Apremilast (CC-10004) is a potent and orally active PDE4 and TNF-α inhibitor with IC50 of 74 nM and 77 nM, respectively.
Int J Mol Sci, 2021, 22(23)12878
J Immunotoxicol, 2021, 18(1):154-162
Acta Pharmaceutica Sinica B, 2021, 10.1016/j.apsb.2021.04.007
S8037 Necrostatin-1 Necrostatin-1 (Nec-1) is a specific RIP1 (RIPK1) inhibitor and inhibits TNF-α-induced necroptosis with EC50 of 490 nM in 293T cells. Necrostatin-1 also blocks IDO and suppresses autophagy and apoptosis.
Int J Mol Sci, 2022, 23(1)506
Cell, 2021, S0092-8674(21)00885-0
Nat Immunol, 2021, 22(9):1107-1117
S8224New PF-3644022

PF-3644022 is a potent freely reversible ATP-competitive inhibitor of MAPKAPK2 (MK2) with an Ki of 3 nM. PF-3644022 also potently inhibits TNFα production with an IC50 of 160 nM.

S8261 GSK583 GSK583 is a highly potent and selective inhibitor of RIP2 kinase with IC50 of 5 nM. GSK583 also inhibits both TNF-α and IL-6 production with IC50 of ~200 nM in explant cultures.
Cancer Res, 2020, canres.530.2020
J Neuroinflammation, 2020, 17(1):364
S8279 Shikonin (C.I. 75535) Shikonin (C.I. 75535, Anchusin, Anchusa acid, Alkanna Red, Isoarnebin 4, NSC 252844), a potent and specific Pyruvate kinase M2 (PKM2) inhibitor, is a major component of zicao (purple gromwell, the dried root of Lithospermum erythrorhizon), a Chinese herbal medicine with various biological activities. It is also an inhibitor of TMEM16A chloride channel activity using cell-based fluorescent-quenching assay. Shikonin exerts an anti-inflammatory effect by inhibiting tumor necrosis factor-α (TNF-α) and prevents activation of nuclear factor-κB (NF-κB) pathway via proteasome inhibition.
J Cancer, 2021, 12(1):76-88
Cancer Sci, 2021, 112(9):3507-3519
J Cell Mol Med, 2021, 10.1111/jcmm.17007
S8484 GSK2982772 GSK2982772 is an ATP competitive receptor-interacting protein-1 (RIP1) kinase (RIPK1) inhibitor with the IC50 value of 16 nM. It has exquisite kinase specificity and excellent activity in blocking many TNF-dependent cellular responses.
Antioxidants (Basel), 2021, 10(9)1347
Mol Cell Biochem, 2021, 10.1007/s11010-021-04136-y
Exp Ther Med, 2021, 21(2):163
S9075 Mulberroside A Mulberroside A, isolated from the ethanol extract of Morus alba roots, is widely employed as an active ingredient in cosmetic products due to its anti-tyrosinase and anti-oxidant activities. Mulberroside A decreases the expressions of TNF-α, IL-1β and IL-6 and inhibits the activation of NALP3, caspase-1 and NF-κB and the phosphorylation of ERK, JNK and p38.
S9090 Corilagin Corilagin, discovered in many medicinal plants such as Phyllanthus speices etc., has multiple activities including anti-oxidative, anti-inflammatory, anti-apoptotic, hepatoprotective and others. It is an inhibitor of TNF-α.
S9129 20(S)-Ginsenoside Rh1 20(S)-Ginsenoside Rh1 (Prosapogenin A2, Sanchinoside B2, Sanchinoside Rh1) is one of major bioactive compounds extracted from red ginseng, which has been increasingly used for enhancing cognition and physical health worldwide. It exhibits potent characteristics of anti-inflammatory, antioxidant, immunomodulatory effects, and positive effects on the nervous system. Ginsenoside Rh1 inhibits the expression of PPAR-γ, TNF-α, IL-6, and IL-1β.
S9184 Forsythoside B Forsythoside B is a phenylethanoid glycoside isolated from the leaves of Lamiophlomis rotata Kudo, a Chinese folk medicinal plant. Forsythoside B has potent neuroprotective effects and has anti-inflammation, antioxidant, and antisepsis properties. Forsythoside B could inhibit TNF-alpha, IL-6, IκB and modulate NF-κB.
S9374 2',5'-Dihydroxyacetophenone 2',5'-Dihydroxyacetophenone (DHAP, 2-Acetylhydroquinone, Quinacetophenone) is a mixture of dihydroxyacetophenone isomers is used in food flavouring. 2',5'-Dihydroxyacetophenone significantly inhibits NO production via the suppression of iNOS expression. 2',5'-Dihydroxyacetophenone significantly decreases levels of the pro-inflammatory cytokines TNF-α and IL-6 by blocking the ERK1/2 and NF-κB signaling pathways.
Pathol Oncol Res, 2019, 25(1):301-309
S9396 Geraniin Geraniin, a hydrolysable polyphenol derived from Nephelium lappaceum L. fruit rind, has been shown to possess significant antioxidant activity in vitro.The IC50 values of TNF-α release inhibition were 43 μM for geraniin.
S9417 Homoplantaginin Homoplantaginin (Hispidulin-7-glucoside), a main flavonoid from a traditional Chinese medicine Salvia plebeia, has anti-inflammatory and anti-oxidant properties. Homoplantaginin inhibits TNF-α and IL-6 mRNA expression, IKKβ and NF-κB phosphorylation.
S9502 Madecassic acid Madecassic acid (Brahmic acid), a natural triterpene first isolated from C. asiatica, has diverse anti-inflammatory and anti-diabetic effects, blocking NF-κB activation in macrophages and causing by iNOS, COX-2, TNF-alpha, IL-1beta and IL-6 inhibition.
A2010 Adalimumab (anti-TNF-alpha) Adalimumab (anti-TNF-alpha) is the first fully human, recombinant IgG1 monoclonal antibody that specifically targets human TNF-alpha, MW: 144.19 KD.
Toxicol In Vitro, 2021, 73:105134
Nature, 2020, 584(7822):608-613
Nature, 2020, 584(7822):608-613
A5046 TNF Receptor II Rabbit Recombinant mAb

TNF Receptor II Antibody detects endogenous levels of total TNF Receptor II.

S2979 CU-T12-9 CU-T12-9 is a specific agonist of Toll-like receptor (TLR) 1/2 with EC50 of 52.9 nM in HEK-Blue hTLR2 SEAP assay. CU-T12-9 activates both the innate and the adaptive immune systems. CU-T12-9 signals through NF-κB and invokes an elevation of the downstream effectors TNF-α, IL-10, and iNOS.
S3865 Taurochenodeoxycholic acid Taurochenodeoxycholic acid (Taurochenodeoxycholate, TCDCA, Chenodeoxycholyltaurine), a bile acid formed in the liver of most species, is used as a cholagogue and choleretic.
Nat Commun, 2021, 12(1):6479
Microbiome, 2019, 7(1):145
S5584 Citronellol Citronellol (Dihydrogeraniol, (±)-β-Citronellol), a constituent of rose and geranium oils, is used in perfumes and insect repellents. Citronellol can cause necrotic apoptosis of NCI-H1299 cells by up-regulating TNF-α, RIP1 / RIP3 activities, and down-regulating caspase-3 / caspase-8 activities. Citronellol also results in a biphasic increase in ROS production at 1 h and at 12 h in NCI-H1299 cells.
S7963 TIC10 (ONC201) TIC10 (ONC201) inactivates Akt and ERK to induce TNF-related apoptosis-inducing ligand (TRAIL) through Foxo3a, possesses superior drug properties: delivery across the blood-brain barrier, superior stability and improved pharmacokinetics. Phase 1/2.
Mol Cell, 2020, 80(6):1104-1122.e9
ACS Chem Biol, 2019, 14(5):1020-1029
Eur J Pharmacol, 2019, 857:172423
S5851 4'-Methoxychalcone 4'-Methoxychalcone, found in citrus, is chalcone derivative that has shown diverse pharmacological properties, including anti-tumor and anti-inflammatory activities. 4'-Methoxychalcone significantly enhanced adipocyte differentiation, in part, by its potent effects on PPARγ activation and by its reverse effect on TNF-α.
S6643 R-7050 R-7050 is a cell permeable TNF-α receptor antagonist and is 2.3-fold more selective for TNF-α-mediated signaling than for that driven by IL-1β.
Research Square, 2021, 10.21203/rs.3.rs-611538/v1
Cancer Sci, 2020, 112(1):168-177
Cell Signal, 2020, 73:109702
S6347New 5'-N-Ethylcarboxamidoadenosine (NECA) 5'-N-Ethylcarboxamidoadenosine (NECA, 5'-(N-Ethylcarboxamido)adenosine, Adenosine-5'N-ethylcarboxamide, 5'-Ethylcarboxamidoadenosine) is a stable, nonselective adenosine receptor agonist. 5'-N-Ethylcarboxamidoadenosine acts via multiple mechanisms including: reducing diabetes-induced oxidative stress, inhibiting gene expression of IL-18, TNF-α and ICAM-1 (intercellular adhesion molecule 1 (CD54)), and blocking activation of the JNK-MAPK pathway.
S7942 Bioymifi Bioymifi, a small-molecule death receptor 5 (DR5) agonist, binds to the extracellular domain(ECD) of DR5 with a Kd of 1.2 μM but showed little binding affinity to the DR4 ECD. It induces DR5 clustering and aggregation, leading to apoptosis.
Front Immunol, 2020, 11:1345
S8133 Resiquimod (R-848) Resiquimod (R-848, S28463) is an immune response modifier that acts as a potent TLR 7/TLR 8 agonist that induces the upregulation of cytokines such as TNF-α, IL-6 and IFN-α. Resiquimod reduces hepatitis C virus (HCV) infection. Phase 2.
Pharmaceutics, 2021, 13(3)365
bioRxiv, 2021, 2021.03.31.437792
Vaccines (Basel), 2020, 15;8(2):E186
S1537 Vadimezan (ASA404) Vadimezan (ASA404, NSC 640488, DMXAA) is a vascular disrupting agents (VDA) and competitive inhibitor of DT-diaphorase with Ki of 20 μM and IC50 of 62.5 μM in cell-free assays, respectively. DMXAA (Vadimezan) is also a STING agonist with potential antineoplastic activity. DMXAA (Vadimezan) potently induces IFN-β but relatively low TNF-α expression in vitro. DMXAA (Vadimezan) has antiviral activity. Phase 3.
Cell, 2022, 185(1):169-183.e19
Yonsei Med J, 2022, 63(1):42-55
J Clin Invest, 2021, e144339
E0130New Apigenin-7-O-glucuronide

Apigenin-7-O-glucuronide (Apigenin-7-glucuronide) is the major flavonoid found in milk thistle. Apigenin 7-o-glucuronide inhibits tumor necrosis factor alpha (TNF-α) and total nitrite release in lipopolysaccharide-activated macrophages.

E0314New JTE-607 Dihydrochloride

JTE-607 Dihydrochloride is a prodrug compound that is converted to an active form by ester hydrolysis. JTE-607 is a multiple cytokine production inhibitor that targets CPSF3 and inhibits pre-mRNA processing. JTE-607 inhibits tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8 and IL-10, from LPS-stimulated human PBMCs, with IC50 values of 11 nM, 5.9 nM, 8.8 nM, 7.3 nM and 9.1 nM, respectively.

S3231New UCB-9260 UCB-9260 is an orally active inhibitor that inhibits TNF signalling by stabilising an asymmetric form of the trimer. UCB-9260 binds TNF with Kd of 13  nM. UCB-9260 also inhibits NF-κB with IC50 of 202 nM after TNF stimulation.
S3515New Benpyrine racemate Benpyrine racemate ((Rac)-Benpyrine) is a potent, highly specific and orally active inhibitor of TNF-α and attenuates TNF-α-induced inflammation, thereby reducing liver and lung injury.
S8224New PF-3644022

PF-3644022 is a potent freely reversible ATP-competitive inhibitor of MAPKAPK2 (MK2) with an Ki of 3 nM. PF-3644022 also potently inhibits TNFα production with an IC50 of 160 nM.

S6347New 5'-N-Ethylcarboxamidoadenosine (NECA) 5'-N-Ethylcarboxamidoadenosine (NECA, 5'-(N-Ethylcarboxamido)adenosine, Adenosine-5'N-ethylcarboxamide, 5'-Ethylcarboxamidoadenosine) is a stable, nonselective adenosine receptor agonist. 5'-N-Ethylcarboxamidoadenosine acts via multiple mechanisms including: reducing diabetes-induced oxidative stress, inhibiting gene expression of IL-18, TNF-α and ICAM-1 (intercellular adhesion molecule 1 (CD54)), and blocking activation of the JNK-MAPK pathway.