tnf-α-in-6

TNF-α-IN-6 is an orally efficacious, allosteric inhibitor of TNFα (K_D = 6.8 nM).

1. Linalool (Linalol), a natural compound of the essential oils, has been shown to have antinociceptive, antimicrobial, and anti-inflammatory properties. 2. Linalool was protected against LPS GalN-induced liver injury through induction of antioxidant defense via Nrf2 activating and reduction inflammatory response via NF-κB inhibition. 3. Linalool biosynthesis and accumulation might be involved in plant defense against bacterial and fungal pathogens and be associated with field resistance to citrus canker. 4. Linalool significantly increased the expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL)-6.

ABzOH is a benzoic acid derivative, similar in structure to non-steroidal anti-inflammatory drugs such as aspirin, with anti-inflammatory, anti-tumor and anti-proliferative effects. ABzOH can not only inhibit the expression of tumor necrosis factor-α (TNF-a), interleukin-1β (IL-1β), interleukin-6 (IL-6) and other pro-inflammatory cytokines, but also inhibit breast cancer, lung cancer and pancreatic cancer.

CU-T12-9 is a potent TLR1 2 agonist(EC50 of 52.9 nM in HEK-Blue hTLR2 SEAP assay). It acts by activating the NFkB pathway, upregulating proinflammatory cytokines, and enhancing TLR1 and TLR2 dimerization.CU-T12-9 activates both the innate and the adaptive immune systems. CU-T12-9 selectively activates the TLR1 2 heterodimer, not TLR2 6. CU-T12-9 signals through NF-κB and invokes an elevation of the downstream effectors TNF-α, IL-10, and iNOS.

Anti-inflammatory agent 42 has anti-inflammatory activity and inhibits the expression of TNF-α and IL-6 in LPS-stimulated macrophages.

MD2-TLR4-IN-1 is a myeloid differentiation protein 2 toll-like receptor 4 (MD2-TLR4) complex inhibitor.

Beclomethasone 17-propionate is a glucocorticoid that is the active metabolite of Beclomethasone dipropionate (BDP). As a glucocorticoid receptor (GR) agonist, 17-BMP has a 13-fold higher affinity than BDP and inhibits the production of pro-inflammatory cytokines, such as CXCL8, TNF-α, and IL-6, thus exerting an anti-inflammatory effect, and it is mainly used in the treatment of asthma and allergic rhinitis.

Manumycin A is an antibiotic with anticancer activity and is a mammalian thioredoxin reductase-1 (TrxR-1) inhibitor.Manumycin A inhibits the production of IL-1β, IL-6, and IL-8 in TNF alpha-stimulated THP-1 cells and peripheral blood mononuclear cells in a dose-dependent manner, inducing apoptosis.

TLR4-IN-1 (compound 3k) demonstrates potent inhibition of RAW264.7 cell viability with an IC 50 value of 1.02 μM. Additionally, it suppresses the release of cytokines TNF-α, IL-1β, and IL-6, and shows anti-inflammatory effectiveness in rat models of rheumatoid arthritis.

Sabialimon P (compound 16), with an IC50 of 18.12 μM, functions as a NO release inhibitor and exhibits anti-inflammatory properties. It effectively diminishes the secretion of TNF-α, iNOS, IL-6, and NF-κB, and suppresses the expression of COX-2 and NF-κB p65 in LPS-induced RAW264.7 cells.

Microtubule destabilizing agent-2 (Compound 21) is an orally active and selective anticancer compound targeting microtubule proteins. It disrupts microtubule stability, inhibiting microtubule polymerization. This agent causes human tumor cells to arrest in the G0 G1 phase and induces apoptosis (Apoptosis) through activation of the Caspase cascade pathway. Additionally, it exhibits anti-inflammatory properties, inhibiting the production of TNF-α and IL-6 in vitro. Microtubule destabilizing agent-2 also suppresses tumor growth in xenograft mice.

PDE1-IN-9 (Compound 7a) is a selective inhibitor of phosphodiesterase 1 (PDE1), targeting PDE1C with an IC50 value of 11 nM. It effectively reduces the mRNA expression of IL-1β, IL-6, TNF-α, and iNOS, while also inhibiting the production of nitric oxide (NO) and reactive oxygen species (ROS). Additionally, PDE1-IN-9 demonstrates good metabolic stability in rat liver microsomes.

COX-2 15-LOX-IN-6 (Compound 5l) is a dual inhibitor of COX-2 and 15-LOX with IC50 values of 0.201 μM and 11.723 μM, respectively. In serum, it suppresses the expression of PGE, TNF-α, IL-6, and iNOS, and demonstrates anti-inflammatory activity in a carrageenan-induced rat edema model.

CB2 receptor agonist 9 (Compound 33) is an orally active agonist of cannabinoid receptor 2 (CB2 receptor) with an EC50 of 16.2 nM. It inhibits the expression of TNF-α, IL-1β, and IL-6, demonstrating anti-inflammatory activity in a DSS-induced acute colitis model in mice.

SDMA p-Hydroxyazobenzene-p′-sulfonate is the p-hydroxyazobenzene-p′-sulfonate form of SDMA. It acts as an inhibitor of endogenous nitric oxide synthase (NO synthase) and serves as an activator of NF-κB, enhancing the expression of IL-6 and TNF-α. This compound remains stable in serum and plasma, making it a potential biomarker for liver and kidney dysfunction.

NF-κB MAPK-IN-2 (compound 14) is a potent inhibitor of NF-κB and MAPK pathways. It effectively reduces the protein expression levels of p-p65, p-IκB, p-p38, p-JNK, and p-ERK. This compound decreases the release of TNF-α and IL-6 induced by LPS and inhibits the nuclear translocation of p65 and c-Fos. NF-κB MAPK-IN-2 shows potential for research in sepsis.

HDAC6degrader-5 (Compound 6) exhibits inhibitory and degradative activity against HDAC6, with an IC50 of 4.95 nM and a DC50 of 0.96 nM. It suppresses the release of TNF-α, IL-1β, and IL-6, and prevents apoptosis in liver cells. Additionally, HDAC6degrader-5 demonstrates anti-inflammatory properties in a mouse model of APAP-induced liver injury.

sEH inhibitor-19 (Compound (R)-14i) is an orally active soluble epoxide hydrolase (sEH) inhibitor with an IC50 of 1.2 nM. This compound suppresses the expression of TNF-α and IL-6 and exhibits anti-inflammatory effects in mouse models of acute pancreatitis and Carrageenan-induced edema.

EGFR-IN-144 (Compound 4B) inhibits EGFR (IC50=0.639 µg mL) and tubulin polymerization (IC50=7.339 µg mL). It exhibits cytotoxicity in various cancer cells with a GI50 at the nanomolar level. EGFR-IN-144 reduces the expression of mTOR, TNF-α, and IL-6, causes G1 S phase cell cycle arrest, and induces apoptosis.

STAT1 3-IN-1 (Compound 6k) is an inhibitor of STAT1 3 phosphorylation. It prevents the phosphorylation and nuclear translocation of STAT1 3. Additionally, STAT1 3-IN-1 inhibits the inflammatory enzymes iNOS and COX-2. This compound exhibits anti-inflammatory properties by reducing pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, without significant cytotoxicity.

CB1R antagonist 2 (Compound 11g) functions as an antagonist of the cannabinoid receptor 1 (CB1R), inhibiting the MAPK NF-κB signaling pathway and exhibiting anti-inflammatory properties. In RAW264.7 cells, it suppresses LPS-induced expression of IL-6, IL-1β, and TNF-α. In murine models, it improves OVA-induced allergic rhinitis.

Acanthoic acid is a pimaradiene diterpene isolated from Acanthopanax koreanum with anti-inflammatory activities. Acanthoic acid downregulates LPS-induced IL-1β, IL-6 and TNF-α production in BALF, attenuates lung histopathologic changes, and inhibits infla

JTE-607 is a cytokine production inhibitor. JTE-607 induces apoptosis accompanied by an increase in p21waf1 cip1 in acute myelogenous leukemia cells.

TG6-129 is an antagonist of the EP2 receptor. TG6-129 suppresses PGE2-induced elevation of cAMP in cells expressing EP2 with an IC50 value of 1.6 µM. TG6-129 reduces the expression of COX-2, IL-1β, IL-6, IL-12, IL-23 and TNF-α induced by the EP2-selective