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

Uses

Different sources of media describe the Uses of 978-62-1 differently. You can refer to the following data:
1. IMD 0354 is an IKKβ (IKK2) inhibitor that blocks NF-κB phosphorylation (IC50 = ~250 nM) and subsequent NF-κB p65 nuclear translocation. It exhibits cardioprotective properties by decreasing 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, suppresses the growth of human breast cancer cells by inducing cell cycle arrest and apoptosis. It induces apoptosis of chronic lymphocytic leukemia cells at 1-10 μM by directly targeting the NF-κB pathway, decreasing expression of anti-apoptotic genes and increasing expression of proapoptotic genes.
2. IMD-0354 has been used to study the effect of NF-κB (nuclear factor) inhibition on differentially expressed in chondrocytes 2. It has also been used to study 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

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

Downstream Products

• 634913-38-5 C₂₉H₂₁ClF₆NO₅P 
• 634913-40-9 C₁₅H₈ClF₆NO₅P^(1-)*Na⁽¹⁺⁾ 
• 634913-39-6 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate 
• 634913-36-3 C₁₇H₁₃ClF₆N₂O₄S 
• 1417658-05-9 2-benzyloxy-N-(3,5-bis-trifluoromethyl-phenyl)-5-chlorobenzamide 
• 1417658-08-2 C₁₅H₈ClF₆NOS 
• 1417795-75-5 C₂₃H₂₁ClF₆N₂O₅ 
• 1417795-55-1 C₂₄H₂₃ClF₆N₄O₆ 
• 1401507-21-8 C₁₉H₁₃ClF₆N₂O₅ 
• 1401460-95-4 C₁₉H₁₅ClF₆N₄O₄*ClH 
• 634913-37-4 C₁₅H₈ClF₆NO₅S 
• 634914-41-3 5-chloro-2-hydroxy-N-[3,5-bis(trifluoromethyl)phenyl]benzamide sodium salt 

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