AZ1495 is a novel, orally active interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor. AZ1495 inhibits the activity of both IRAK4 (IC50=5nM) and IRAK1 (IC50=23nM). AZ1495 can be used in research related to diffuse large B-cell lymphoma (DLBCL)[1-2].
In vitro, AZ1495 (1μM) was used to treat human corneal epithelial cells (HCECs) under hypertonic conditions for 24 hours. AZ1495 significantly inhibited the expression of the IRAK1 protein and its downstream inflammatory and apoptotic factors, and enhanced cell viability[1]. AZ1495 (1nM-100μM) was used to treat OCI-LY10 cells for 3 days, effectively inhibiting the activation of the NF-κB pathway (e.g., by reducing p-IκBα levels) and inducing cell death[2].
In vivo, in an OCI-LY10 xenograft mouse model, AZ1495 (12.5mg/kg; administered orally once daily; for 51 consecutive days) alone was shown to inhibit tumor growth. When AZ1495 was combined with Ibrutinib (12mg/kg; administered orally once daily), AZ1495 led to tumor regression[2].
References:
[1] Liu Y, Jiang Y, Song C, et al. The role of miR-146a/IRAK1/JNK1 pathway in mediating the effects of Yiqi Congming decoction on dry eye: A mechanistic study in rat models. J Ethnopharmacol. 2025 May 12;347:119698.
[2] Scott JS, Degorce SL, Anjum R, et al. Discovery and Optimization of Pyrrolopyrimidine Inhibitors of Interleukin-1 Receptor Associated Kinase 4 (IRAK4) for the Treatment of Mutant MYD88L265P Diffuse Large B-Cell Lymphoma. J Med Chem. 2017 Dec 28;60(24):10071-10091.
AZ1495是一种新型的、具有口服活性的白细胞介素-1受体相关激酶4（IRAK4）抑制剂。AZ1495可抑制IRAK4（IC50=5nM）和IRAK1（IC50=23nM）的活性。AZ1495可用于弥漫性大B细胞淋巴瘤（DLBCL）的相关研究[1-2]。
在体外，AZ1495（1μM）处理高渗环境下的人角膜上皮细胞（HCECs）24小时，显著抑制了IRAK1蛋白的表达及其下游炎症因子和凋亡因子的表达，并增强了细胞活力[1]。AZ1495（1nM-100μM）处理OCI-LY10细胞3天，能有效抑制NF-κB通路的激活（如降低p-IκBα水平），并诱导细胞死亡[2]。
在体内，在OCI-LY10异种移植瘤小鼠模型中，AZ1495（12.5mg/kg；每日一次口服给药；连续处理51天）单独处理，能够抑制肿瘤生长抑制；当AZ1495与Ibrutinib（12mg/kg；每日一次口服给药）联合使用时，能够导致肿瘤消退[2]。