| Description | IRAK-1-4 Inhibitor I is a dual inhibitor of IRAK4 and IRAK1. |
| In vitro | IRAK-1-4 Inhibitor I has IC50 greater than the highest concentration tested (10 μM) against a panel of 27 other kinases, including the most closely homologous (outside of the IRAK family) Lck and pp60SRC. Additionally, IRAK-1-4 Inhibitor I does not show any signs of cytotoxicity in a 72 h proliferation assay in HeLa cells (ED50>30 μM). Significant inhibition of IRAK-1 is observed with IRAK-1-4 Inhibitor I (IRAK-1 IC50=0.3 μM)[1]. IRAK-1/4 inhibitor eliminates the LPS-induced increases in Bcl10, NF-κB, and IL-8. IRAK-1/4 mediates LPS-induced IL-8 activation and functions upstream of Bcl10. The LPS-induced increase in Bcl10 declines by 73% (from 5.18±0.22 to 2.36±0.08 ng/mL), and the IL-8 response decline by 60% (from 2.64±0.31 to 1.14±0.08 ng/mL)[2]. |
| Cell experiments | IRAK-1-4 Inhibitor I is dissolved in DMSO and stored, and then diluted with appropriate media before use[2]. NCM460 cells, grown in 24-well plates, are incubated with 50 μM IRAK-1/4 inhibitor for 2 h. After 2 h, the media are changed, and new media with or without LPS (10 ng/mL) added. Treatment is terminated at 6 h, and spent media and cells are collected for IL-8 and other assays[2]. |
| Target activity | IRAK1:0.2 μM, IRAK4:0.3 μM |
| Synonyms | IRAK-1/4 Inhibitor I, IRAK-1/4 Inhibitor |
| molecular weight | 395.41 |
| Molecular formula | C20H21N5O4 |
| CAS | 509093-47-4 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 8.13 mg/mL (20.55 mM), Sonication is recommended. |
| References | 1. Powers JP, et al. Discovery and initial SAR of inhibitors of interleukin-1 receptor-associated kinase-4. Bioorg Med Chem Lett. 2006 Jun 1;16(11):2842-2845. 2. Bhattacharyya S, et al. Bcl10 mediates LPS-induced activation of NF-kappaB and IL-8 in human intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2007 Aug;293(2):G429-37. 3. Wu X, Xu M, Liu Y, et al. Dual Pharmacological Inhibition of IRAK1 and IRAK4 Prevents LPS Induced Monocyte Adhesion to Endothelial Cells[J]. bioRxiv. 2021 |