inos-in-1

iNOs-IN-1 (YPW) is a potent inhibitor of inducible nitric oxide synthase (iNOS) with anti-inflammatory effects, significantly inhibiting IL-6 and iNOS expression in a dose-dependent manner in murine macrophages, and also inhibiting LPS-induced NO generation.

iNOS-IN-14 (3-bromo-1H-indazole-7-carbonitrile) is a potent nitric oxide synthase (NOS) inhibitor that inhibits the NADPH oxidase activity of nNOS.

Compound AuL9, also known as iNOS/TopoI-IN-1, is a multi-target hybrid molecule possessing anti-tumor, anti-inflammatory, and antioxidant properties. This compound effectively inhibits the growth of MCF-7 and MDA MB-231 breast cancer cells in vitro, exhibiting IC50 values of 3.5 μM and 6.3 μM respectively. It also prompts DNA damage and apoptosis in these cells by inhibiting human topoisomerase I (TopoI) with a K_i of 2.72 μM. Additionally, iNOS/TopoI-IN-1 reduces the expression of iNOS by suppressing the activation of NF-kB, with a K_i of 1.49 μM.

iNOS/COX-2-IN-1 (Compound 12e) is an inhibitor of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). By inhibiting the NF-κB and MAPKs signaling pathways, iNOS/COX-2-IN-1 exhibits anti-inflammatory effects.

iNOS/PGE2-IN-1 is an iNOS/PGE2 inhibitor and a potent anti-inflammatory agent. iNOS/PGE2-IN-1 exhibits an inhibitory effect on LPS-induced NO production and has a low ulcerogenic potential.

NOS-IN-1 (2-Imino-4-methylpiperidine acetate) is a potent and orally active inhibitor of NO synthase (NOS) isoforms. NOS-IN-1 exhibits IC50s of 0.1 μM, 0.2 μM, and 1.1μM for human iNOS (hiNOS), hnNOS and heNOS, respectively.

S-Methylisothiourea sulfate ((S)-Methylisothiourea sulfate) is a potent and selective inhibitor of iNOS and exerts beneficial effects in rodent models of septic shock[1].

Methylguanidine (MG) is a guanidine compound deriving from protein catabolism. It is also a product of putrefaction. Methylguanidine is a suspected uraemic toxin that accumulates in renal failure, however it also exhibits anti-inflammatory effects. Methyl

Bisdemethoxycurcumin (Curcumin III) is a natural demethoxy derivative of curcumin. It is a potent activator of macrophage phagocytosis, interacting with 1α, 25-dihydroxy vitamin D3 to stimulate amyloid-β clearance by macrophages (optimal stimulation at 100 nM BDMC) [1]. More stable than curcumin in physiological media, BDMC suppresses proliferation of cancer cells [2]. It down-regulates the transcriptional coactivator p300, suppressing the Wnt/β-catenin pathway, and inhibits LPS induction of iNOS expression [3].

Radicicol (Monorden) is an antifungal antibiotic and a potent inhibitor of heat shock protein 90 (Hsp90), which leads to the degradation of Hsp90 by the proteasome by binding to its ATP-binding pocket. In addition, Radicicol inhibits the growth and proliferation of several tumor cell lines. It also has anti-malarial activity and acts as an inhibitor of adipose- and obesity-related proteins (FTO). Radicicol inhibits iNOS gene expression by blocking the p38 kinase signaling pathway and NF-kB/Rel

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.

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.

TLR4/JNK/NF-κB-IN-1 (Racemic-11k) is an inhibitor of TLR4, JNK, and NF-κB. It suppresses NO production in LPS-stimulated RAW264.7 cells with an IC50 of 23.2 µM. By inhibiting TLR4 expression and reducing JNK phosphorylation, TLR4/JNK/NF-κB-IN-1 prevents NF-κB activation. This leads to a decrease in the transcription of inflammation-related genes, reducing the expression of iNOS and COX-2, and the production of inflammatory mediators such as NO, PGE2, and TNF-α, thereby exhibiting anti-inflammatory activity. TLR4/JNK/NF-κB-IN-1 holds potential in the study of inflammatory diseases, including rheumatoid arthritis and various other inflammatory conditions.

PPM-18 (NSC 73233) is a potent anti-inflammatory agent which inhibits nitric oxide synthase expression. PPM-18 is a potent inhibitor of iNOS expression by blocking the binding of NF-κB to promoter [1]. PPM-18 is an analog of Vitamin K remarkably suppressed the proliferation and induced apoptosis in bladder cancer cells [2].

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.

Momordin Ic (Momordin 1c) might represent a potential anticancer activity, by inducing apoptosis through oxidative stress-regulated mitochondrial dysfunction involving the MAPK and PI3K-mediated iNOS and HO-1 pathways. Also, Momordin Ic accelerates gastrointestinal transit partially by stimulating synthesis of 5-HT to act through 5-HT(2), which, in turn, increases synthesis of prostaglandins.

Amentoflavone (3',8''-Biapigenin), as a potent inhibitor of CYP3A4 and CYP2C9, can interact with many other medications. CYP3A4 and CYP2C9 are proteins used for drug metabolism in the body. Amentoflavone also is an inhibitor of human cathepsin B. It has antimalarial activity in trials significant affinities towards the Delta-1, kappa opioid receptors (as an antagonist) and binds to benzodiazepine receptors. Amentoflavone may be a potential lead for a new type of anti-inflammatory agents having the dual inhibitory activity of group II phospholipase A2 and cyclooxygenase. Amentoflavone and quercetin differentially exerted suppression of PGE2 biosynthesis via downregulation of COX-2/iNOS expression.

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

NOS1-IN-1(nNOS Inhibitor I) is a potent, selective and cell permeable nNOS inhibitor (Ki: 120 nM).NOS1-IN-1 has a Ki value of 39 μM for eNOS and 325 μM for iNOS.NOS1-IN-1 can be used for the study of neurological disorders such as cerebral palsy.

Highly selective and potent inhibitor of nNOS (Ki = 57 nM). Displays 3158-fold and 149-fold selectivity over iNOS and eNOS respectively. Hypotensive in vivo. Kakoki et al (2001) The influence of nitric oxide synthase 1 on blood flow and interstitial nitric oxide in the kidney. Am.J.Physiol.Regul.Integr.Comp.Physiol. 281 R91 PMID:11404282 |Zhang et al (1997) Potent and selective inhibition of neuronal nitric oxide synthase by Nω-propyl-L-arginine. J.Med.Chem. 40 3869 PMID:9397167

Rosarin has anti-inflammatory and neuroprotective effects. Rosarin supresses the expression of the proinflammatory factors iNOS, IL-1 β, and TNF- α in the kidney and prefrontal cortex of brain in mice .

(Rac)-Zevaquenabant ((Rac)-MRI-1867, compound 6b) is a potent and selective antagonist of cannabinoid receptor type 1 (CB1R) and inducible nitric oxide synthase (iNOS), with a binding affinity (Ki) of 5.7 nM for CB1R. It holds promise as an investigative tool in liver fibrosis research due to these characteristics.

1. Protostemonine has anti-inflammatory activity, it effectively attenuates LPS-induced inflammatory responses in vitro and in vivo; the beneficial effects are associated with the decreased phosphorylation of MAPK and AKT and the reduced expression of pro

1. Cornuside (Comuside) has immunomodulatory activity . 2. Cornuside suppresses expression levels of cytokine-induced proinflammatory and adhesion molecules in the human endothelial cells. 3. Cornuside can treat myocardial I/R and protect the liver from CCl4-induced acute hepatotoxicity, by reducing oxidative stress and suppressing inflammatory responses. 4. Cornuside has anti-inflammatory activity by downregulations of iNOS and COX-2 due to NF-κB inhibition as well as the negative regulation of ERK1/2, p38, and JNK1/2 phosphorylations in RAW 264.7 cells. 5. Cornuside has protective potential against cerebral ischemic injury, may be due to the suppression of intracellular Ca(2+) elevation and caspase-3 activity, and improvements in mitochondrial energy metabolism and antioxidant properties.