1. IRAK
  2. IRAK inhibitor 4

IRAK inhibitor 4 

Cat. No.: HY-13278 Purity: 99.77%
Handling Instructions

IRAK inhibitor 4 is an interleukin-1 receptor associated kinase 4(IRAK4) inhibitor.

For research use only. We do not sell to patients.

IRAK inhibitor 4 Chemical Structure

IRAK inhibitor 4 Chemical Structure

CAS No. : 1012104-68-5

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10 mM * 1 mL USD 1098 In-stock
Estimated Time of Arrival: December 31
5 mg USD 804 In-stock
Estimated Time of Arrival: December 31
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Based on 1 publication(s) in Google Scholar

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Description

IRAK inhibitor 4 is an interleukin-1 receptor associated kinase 4(IRAK4) inhibitor.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

620.66

Formula

C₃₃H₃₅F₃N₆O₃

CAS No.

1012104-68-5

SMILES

OC1CCC(N2C3=C(C=C(C=C3)C(NCCC(C)C)=O)N=C2NC4=NNC5=C4C=C(C=C5)C6=CC=CC=C6OC(F)(F)F)CC1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 12.5 mg/mL (20.14 mM; Need ultrasonic)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.6112 mL 8.0559 mL 16.1119 mL
5 mM 0.3222 mL 1.6112 mL 3.2224 mL
10 mM 0.1611 mL 0.8056 mL 1.6112 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 1.25 mg/mL (2.01 mM); Clear solution

  • 2.

    Add each solvent one by one:  10% DMSO    90% corn oil

    Solubility: ≥ 1.25 mg/mL (2.01 mM); Clear solution

*All of the co-solvents are provided by MCE.
References
Cell Assay
[1]

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.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

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.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References

Purity: 99.77%

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Keywords:

IRAK inhibitor 4IRAK inhibitor4IRAK inhibitor-4IRAKInterleukin-1 receptor associated kinaseIL-1R associated kinaseInhibitorinhibitorinhibit

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Product Name:
IRAK inhibitor 4
Cat. No.:
HY-13278
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