JH-XIII-05

JH-XIII-05 is an experimental bifunctional proteolysis-targeting chimera (PROTAC) designed to induce degradation of interleukin-1 receptor-associated kinases 1 and 4 (IRAK1 and IRAK4), key mediators of MYD88-driven pro-survival signaling in B-cell malignancies such as Waldenström macroglobulinemia and activated B-cell–type diffuse large B-cell lymphoma. It is built on a dual IRAK1/4 inhibitor scaffold (JH-XI-82-01) and linked to an E3 ligase–recruiting moiety, enabling both potent kinase inhibition and selective proteasomal degradation of IRAK1/4, with low-nanomolar antiproliferative activity and induction of apoptosis in MYD88-mutant lymphoma cell lines, including those harboring BTK C481 mutations.[2][4] Preclinical studies show superior cytotoxicity compared with the parent inhibitor, favorable subcutaneous pharmacokinetics in mouse models with exposures exceeding cellular IC50 values, and synergistic activity when combined with the BTK inhibitor ibrutinib or the BCL2 inhibitor venetoclax in MYD88-mutated lymphoma models.[2]

Other names

JH-XIII-05-1JH-XIII05-1JH-XIII 05-1