JH-I-25

JH-I-25 is a potent, small-molecule dual inhibitor of Interleukin-1 receptor-associated kinase 1 (IRAK1) and Interleukin-1 receptor-associated kinase 4 (IRAK4). Developed at the Dana-Farber Cancer Institute, it inhibits IRAK1 and IRAK4 with IC50 values of 9.3 nM and 17.0 nM, respectively. The compound serves as a critical chemical probe for investigating the Toll-like receptor (TLR) and Interleukin-1 receptor (IL-1R) signaling pathways, which are often dysregulated in MYD88-mutated malignancies. By blocking the kinase activity of both IRAK1 and IRAK4, JH-I-25 disrupts the signal transduction required for NF-κB activation, thereby inhibiting pro-survival signaling in B-cell lymphomas such as Activated B-Cell Diffuse Large B-Cell Lymphoma (ABC-DLBCL) and Waldenström Macroglobulinemia. While it has been used as a scaffold for the development of more selective IRAK inhibitors and proteolysis-targeting chimeras (PROTACs), JH-I-25 itself is classified for research use only and is not currently used in human clinical trials.

Other names

JH-I-25JH-I25JH-I 25