978-62-1

Basic information

• Product Name: IMD-0354
• Synonyms: Benzamide, N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxy-;N-[3,5-Bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide IMD0354;IMD-0354, 99%, a synthetic selective NF-kB inhibitor
• CAS NO: 978-62-1
• Molecular Formula: C₁₅H₈ClF₆NO₂
• Molecular Weight: 383.674
• Product Categories: Intracellular Signaling;Inhibitors;NF-kB
• Mol File: 978-62-1.mol
• Article Data: 20

Chemical Properties

• Boiling Point: 323.1 °C at 760 mmHg
• Flash Point: 149.2 °C
• Appearance: /
• Density: 1.561
• Vapor Pressure: 0.000141mmHg at 25°C
• Refractive Index: 1.543
• Storage Temp.: −20°C
• Solubility: Solubility: DMSO (5 mg/ml) or Ethanol (1 mg/ml).
• PKA: 7.61±0.43(Predicted)
• Sensitive: Light Sensitive
• CAS DataBase Reference: IMD-0354(CAS DataBase Reference)
• NIST Chemistry Reference: IMD-0354(978-62-1)
• EPA Substance Registry System: IMD-0354(978-62-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 978-62-1(Hazardous Substances Data)

Usage

Description

IMD-0354 is an IKKβ (IKK2) inhibitor that blocks NF-κB phosphorylation and subsequent NF-κB p65 nuclear translocation. It is a promising compound with potential applications in various fields due to its ability to modulate NF-κB signaling pathways.
Used in Pharmaceutical Industry:
IMD-0354 is used as a cardioprotective agent for decreasing the expression of P-selectin and ICAM-1 in the vasculature and blocking cardiomyocyte IL-1β and MCP-1 production, resulting in suppressed neutrophil accumulation in a rat model of ischemia/reperfusion injury.
IMD-0354 is used as an anticancer agent for suppressing the growth of human breast cancer cells by inducing cell cycle arrest and apoptosis.
IMD-0354 is used as an inducer of apoptosis in chronic lymphocytic leukemia cells at 1-10 μM by directly targeting the NF-κB pathway, decreasing the expression of anti-apoptotic genes, and increasing the expression of pro-apoptotic genes.
Used in Research Applications:
IMD-0354 is used as a research tool for studying the effect of NF-κB inhibition on differentially expressed in chondrocytes 2.
IMD-0354 is used as a research tool for studying the role of NF-κB signaling in tumor necrosis factor-induced certain transcription factors expression using human primary fibroblasts.

Biological Activity

Inhibitor of I κ B kinase-2 (IKK-2, IKK- β ) that blocks NF- κ B nuclear translocation. Attenuates myocardial ischemia/reperfusion injury by decreasing expression of adhesion molecules ICAM-1 and P-selectin and inhibiting cytokine and chemokine production in cardiomyocytes. Induces G 0 /G 1 cell cycle arrest and apoptosis in HMC-1? and breast cancer cells.

Biochem/physiol Actions

IMD-0354 acts as an inhibitor by inhibiting the phosphorylation of the NF-κB (nuclear factor) and its translocation into the nucleus. It blocks IκBα phosphorylation (IC50 ~ 250 nM). Cardioprotectant, that reduces IL-1β and MCP-1 production (IC50 < 1 μM) in cardiomyocytes. IMD-0354 affects angiogenesis, which has been observed in human umbilical vein endothelial cells. It prevents tube formation and migration of the cells. In vivo studies also prove that IMD-0354 inhibits retinal vessel growth. IMD-0354 also acts as an inhibitor of Aquaporin 4 (AQP4) inhibitor (IC50 0.2μM) with no inhibitory potency to IKK-β. [4]

in vitro

imd-0354, at the concentration of less than 5 m, down-regulated the expression of nf-κb and blocked the translocation of nf-κb to the nucleus in hmc-1 cells. study from hmc-1 cells also showed that imd-0354 inhibited cell proliferation in a time and dose dependent manner. in addition, imd-0354 at the concentration of 0.5 μm inhibited the proliferation of ic-2g559 cells and ic-2v814 cells. this agent was also reported to arrest the cell cycle at the g0/g1 phase and decreased the ratio of cells in s and g2/m phases in hmc-1 cells. 1 μm imd-0354 was reported to decrease cyclin d3 expression and reduce prb phosphorylation level in a time-dependent manner in hmc-1 cells. [1]

in vivo

a study from lungs of ova-sensitized mice showed that 5 mg/kg imd-0354 significantly inhibited nf-κb, although the magnitude of inhibition is lower than that caused by 20 mg/kg imd-0354. 20 mg/kg imd-0354 ameliorated airway hyper-responsiveness and decreased the numbers of bronchial eosinophils and mucus-producing cells in ova-sensitized mice. in addition, the total numbers of cells and eosinophils was also reduced by imd-0354 in ova-sensitized mice. moreover, imd-0354 suppressed the production of th2 cytokines inclusing il-5, il-13 and eotaxin in the airways and/or lungs of ova-sensitized mice, whereas it did not alter the restoration of th1 cytokines under the same experimental conditions. [2]

IC 50

imd-0354 showed anti-tumor effect on seven hematologic malignancy cells with ic50 ranged from 0.1m to 0.6 m.

references

[1]tanaka a, konno m, muto s, kambe n, morii e, nakahata t, itai a and matsuda h. a novel nf-kappab inhibitor, imd-0354, suppresses neoplastic proliferation of human mast cells with constitutively activated c-kit receptors. blood. 2005 mar; 105(6): 2324-31. [2]sugita a, ogawa h, azuma m, muto s, honjo a, yanagawa h, nishioka y, tani k, itai a and sone s. antiallergic and anti-inflammatory effects of a novel i kappab kinase beta inhibitor, imd-0354, in a mouse model of allergic inflammation. int arch allergy immunol. 2009; 148(3): 186-98.[3]verstrepen l and beyaert r. receptor proximal kinases in nf-κb signaling as potential therapeutic targets in cancer and inflammation. biochem pharm. 2014; 92: 519-29.

InChI:InChI=1/C15H8ClF6NO2/c16-9-1-2-12(24)11(6-9)13(25)23-10-4-7(14(17,18)19)3-8(5-10)15(20,21)22/h1-6,24H,(H,23,25)

Upstream product

• 321-14-2 5-chloro-2-hydroxybenzoic acid 
• 328-74-5 3,5-Bis-(trifluoromethyl)aniline 
• 15216-81-6 5-chloro-2-hydroxybenzoyl chloride 
• 3438-16-2 5-chloro-2-methoxybenzoic acid 

Downstream Products

• 634913-38-5 C₂₉H₂₁ClF₆NO₅P 
• 634914-41-3 5-chloro-2-hydroxy-N-[3,5-bis(trifluoromethyl)phenyl]benzamide sodium salt 
• 634913-37-4 C₁₅H₈ClF₆NO₅S 
• 1401460-95-4 C₁₉H₁₅ClF₆N₄O₄*ClH 
• 1401507-21-8 C₁₉H₁₃ClF₆N₂O₅ 
• 1417795-55-1 C₂₄H₂₃ClF₆N₄O₆ 
• 1417795-75-5 C₂₃H₂₁ClF₆N₂O₅ 
• 1417658-08-2 C₁₅H₈ClF₆NOS 
• 1417658-05-9 2-benzyloxy-N-(3,5-bis-trifluoromethyl-phenyl)-5-chlorobenzamide 

Relevant articles and documents

SALICYLAMIDE DERIVATIVES AND RELATED METHODS OF MAKING

Certain embodiments describe antiviral compounds and related methods of using such compounds.

Discovery and Structure Relationships of Salicylanilide Derivatives as Potent, Non-acidic P2X1 Receptor Antagonists

Antagonists for the ATP-gated ion channel receptor P2X1 have potential as antithrombotics and for treating hyperactive bladder and inflammation. In this study, salicylanilide derivatives were synthesized based on a screening hit. P2X1 antagonistic potency was assessed in 1321N1 astrocytoma cells stably transfected with the human P2X1 receptor by measuring inhibition of the ATP-induced calcium influx. Structure-activity relationships were analyzed, and selectivity versus other P2X receptor subtypes was assessed. The most potent compounds, N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (1, IC50 0.0192 μM) and N-[3,5-bis(trifluoromethyl)phenyl]-4-chloro-2-hydroxybenzamide (14, IC50 0.0231 μM), displayed >500-fold selectivity versus P2X2 and P2X3, and 10-fold selectivity versus P2X4 and P2X7 receptors, and inhibited collagen-induced platelet aggregation. They behaved as negative allosteric modulators, and molecular modeling studies suggested an extracellular binding site. Besides selective P2X1 antagonists, compounds with ancillary P2X4 and/or P2X7 receptor inhibition were discovered. These compounds represent the first potent, non-acidic, allosteric P2X1 receptor antagonists reported to date.

2-Hydroxy-N-Phenylbenzamides and their esters inhibit acetylcholinesterase and Butyrylcholinesterase

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