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]. The IRAK-1/4 inhibitor suppresses LPS-induced elevations in Bcl10, NF-κB, and IL-8. It mediates the LPS-induced activation of IL-8 and operates upstream of Bcl10. Following treatment, Bcl10 levels decrease by 73% (from 5.18±0.22 to 2.36±0.08 ng/mL), and IL-8 levels drop by 60% (from 2.64±0.31 to 1.14±0.08 ng/mL)[2].
体外研究
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].
The IRAK-1/4 inhibitor suppresses LPS-induced elevations in Bcl10, NF-κB, and IL-8. It mediates the LPS-induced activation of IL-8 and operates upstream of Bcl10. Following treatment, Bcl10 levels decrease by 73% (from 5.18±0.22 to 2.36±0.08 ng/mL), and IL-8 levels drop by 60% (from 2.64±0.31 to 1.14±0.08 ng/mL)[2].
作用机制
IRAK-1-4 Inhibitor I plays the role of IRAK-4 inhibitor by binding with acyl-2-aminobenzimidazole scaffold that represents a unique kinase binding motif.
IRAK-1-4 Inhibitor I 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Malme-3M
2.5 μM
48 h
Inhibition of IRAK-1,-4 signaling enhanced cell apoptosis, with more significant effects when combined with vinblastine
Cancer Res. 2012 Dec 1;72(23):6209-16.
A375
2.5 μM
48 h
Inhibition of IRAK-1,-4 signaling enhanced cell apoptosis, with more significant effects when combined with vinblastine
Cancer Res. 2012 Dec 1;72(23):6209-16.
NCM460 cells
50 μM
2 h
To evaluate the effect of IRAK1/4 inhibitor on DSS-induced IL-8 secretion. Results showed that IRAK1/4 inhibitor had no effect on DSS-induced IL-8 secretion.
Inflamm Bowel Dis. 2009 May;15(5):673-83.
SK-OV-3 ovarian cancer cells
10 µM
24 h
Evaluate the effect of HS-243 on cancer cell survival, showing that HS-243 alone inhibited cell survival by 13%, and in combination with IL-1β, it inhibited cell survival by 46%.
J Biol Chem. 2020 Feb 7;295(6):1565-1574.
AN3-CA pancreatic cancer cells
10 µM
24 h
Evaluate the effect of HS-243 on cancer cell survival, showing that HS-243 alone inhibited cell survival by 21%, and in combination with IL-1β, it inhibited cell survival by 33%.
J Biol Chem. 2020 Feb 7;295(6):1565-1574.
THP-1 human macrophages
10 µM
24 h
Evaluate the effect of HS-243 on inflammatory responses in macrophages after LPS stimulation, showing that HS-243 significantly inhibited the secretion of IL-8, CD14, GRO-α, MIP-1α, MIP-3α, uPAR, Osteopontin, MMP-9, MCP-1, I-TAC, TIM-3, IP-10, GDF-15, and RANTES.
J Biol Chem. 2020 Feb 7;295(6):1565-1574.
human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS)
10 µM
24 h
Evaluate the effect of HS-243 on cytokine/chemokine responses after LPS stimulation, showing that HS-243 significantly inhibited the expression of CCL5, CXCL12, MIF, and IL-18.
J Biol Chem. 2020 Feb 7;295(6):1565-1574.
bone marrow-derived dendritic cells (BMDCs)
50 μM
2 h
Blocking IRAK1/4 signaling significantly reduced S. pneumoniae-induced IL-23 production and completely abolished the inhibitory effects of morphine on IL-23 production.
J Biol Chem. 2011 Mar 25;286(12):10225-32.
IRAK-1-4 Inhibitor I 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NSG mice
A375 melanoma xenograft model
Intratumoral injection
35 mg/kg
Every 2 days for 5 days
Combination therapy significantly delayed tumor growth and prolonged survival
Tags:
IRAK-1-4 Inhibitor I | 509093-47-4 | IRAK-1/4 Inhibitor I | IRAK | IRAK Inhibitor | Immunology/Inflammation | IRAK | 仅供科研使用 | AmBeed-信号通路专用抑制剂
| IRAK-1-4 Inhibitor I 纯度/质量文件
| IRAK-1-4 Inhibitor I 生物活性
| IRAK-1-4 Inhibitor I 动物研究
| IRAK-1-4 Inhibitor I 参考文献
| IRAK-1-4 Inhibitor I 实验方案
| IRAK-1-4 Inhibitor I 技术信息
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