AZ1495

AZ1495 is a preclinical, orally active small-molecule inhibitor of interleukin‑1 receptor–associated kinases, initially developed by AstraZeneca for hematologic malignancies driven by dysregulated Toll‑like receptor and MYD88 signaling, such as non‑Hodgkin lymphoma and primary CNS lymphoma. Biochemically, AZ1495 potently inhibits IRAK4 and also inhibits IRAK1 in the low‑nanomolar range, suppressing downstream NF‑κB activation and inflammatory cytokine production in cellular and intracranial lymphoma models. Preclinical studies have demonstrated good CNS penetration, dose‑dependent growth inhibition of MYD88 L265P‑mutant lymphoma cells, delayed progression of CNS lymphoma, and extended overall survival in mouse models, but the compound has not advanced beyond preclinical development.