IRAK inhibitor 4
Modify Date: 2024-01-02 09:10:40
IRAK inhibitor 4 structure
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Common Name | IRAK inhibitor 4 | ||
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| CAS Number | 1012104-68-5 | Molecular Weight | 620.66500 | |
| Density | N/A | Boiling Point | N/A | |
| Molecular Formula | C33H35F3N6O3 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of IRAK inhibitor 4IRAK inhibitor 4 is an interleukin-1 receptor associated kinase 4(IRAK4) inhibitor. |
| Name | 1-(4-hydroxycyclohexyl)-N-(3-methylbutyl)-2-[[5-[2-(trifluoromethoxy)phenyl]-1H-indazol-3-yl]amino]benzimidazole-5-carboxamide |
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| Synonym | More Synonyms |
| Description | IRAK inhibitor 4 is an interleukin-1 receptor associated kinase 4(IRAK4) inhibitor. |
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| Related Catalog | |
| In Vitro | Lack of IRAK-4 impairs the production of proinflammatory mediators by macrophages and DCs in response to M. bovis and M. tuberculosis. IRAK-4-/- cells stimulated with E. coli LPS display delayed activation kinetics of all signaling proteins analyzed, and exhibit dramatically reduced p65 phosphorylation[1]. IRAK1/4 (20 μM) has an inhibitory effect on LPS mediated IL-6 production. IRAK1/4 inhibitor do not decrease p38 phosphorylation in AMs. Combination of IRAK1/4 and Rip2 inhibitors inhibits TLR2-mediated cytokine production in sarcoidosis PBMCs and AMs[2]. IRAK4 is overexpressed and activated in T-ALL. IRAK4 mRNA level is elevated in T-ALL cells from patients compared with the levels detected in thymic T cells or T cells from peripheral blood[3]. |
| In Vivo | IRAK-4-/- mice exhibit a greatly reduced survival rate following aerosol infection compared with IRAK-4+/+ or IRAK-4+/- mice. IRAK-4-/- mice show increased bacterial burden in all organs at 15, 30, and 60 d postinfection[1]. MCL1, but not BCL-xL, overrides the therapeutic effects of combinatorial IRAK1/4 inhibitor and ABT-737 therapy in vivo[3]. |
| Cell Assay | THP-1 cells are grown in RPMI 1640 medium supplemented with 2 mM L-glutamine, 10% heat-inactivated FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin. For monocytic differentiation, cells are seeded in 24-well flat-bottom culture plates at a density of 5×105 cells/well and allowed to adhere and differentiate for 48 h at 37°C in the presence of 100 nM PMA. THP-1 cells are incubated with 0.1 or 1 μM IRAK-4 inhibitor (IRAK inhibitor 1) for 45 min and then stimulated with M. bovis BCG Moreau (MOI 5:1) or E. coli LPS (1 μg/mL). Culture supernatants are collected after 24 h of stimulation and assayed for the concentrations of human TNF-α or IL-12/23p40 by ELISA. For Western blot analysis, cells are incubated with IRAK-4 inhibitor, in the same concentrations described above, for 45 min and then stimulated with M. bovis BCG Moreau (MOI 5:1) or E. coli LPS (1 μg/mL) for 30 min. The cells are then processed for Western blot assay, as described below. |
| Animal Admin | To evaluate IRAK-4 involvement in mycobacterial infection, IRAK-4+/+ (wild-type), IRAK-4+/- (heterozygous), and IRAK-4-/- (IRAK-4-knockout) mice are used. Eight-week-old mice are infected i.v. with 1×106 CFU of M. bovis strain Moreau. The bacterial loads in the spleens, livers, and lungs are determined at 15, 30, and 60 d postinfection. Briefly, the organs are collected aseptically and homogenized in distilled water that contained 0.05% Tween 80. Serial dilutions of the resulting suspensions are plated on Middlebrook 7H11 agar medium supplemented with 10% oleic acid-albumin-dextrose-catalase, and CFU are counted following a 21-d incubation at 37°C and 5% CO2. |
| References |
| Molecular Formula | C33H35F3N6O3 |
|---|---|
| Molecular Weight | 620.66500 |
| Exact Mass | 620.27200 |
| PSA | 123.81000 |
| LogP | 7.47040 |
| Storage condition | 2-8℃ |
| IRAK inhibitor 4 |
| 2-(5-(2-(trifluoromethoxy)phenyl)-1H-indazol-3-ylamino)-1-(4-hydroxycyclohexyl)-N-isopentyl-1H-benzo[d]imidazole-5-carboxamide |
| CS-0606 |
| 1-(4-hydroxycyclohexyl)-2-[5-(2-trifluoromethoxyphenyl)-1H-indazol-3-ylamino]-1H-benzoimidazole-5-carboxylic acid (3-methylbutyl)amide |