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IRAK inhibitors act on interleukin-1 receptor-associated kinases (IRAKs), kinases of innate immune receptor signaling. IRAK was cloned in 1996 as a serine/threonine kinase that associates with the interleukin-1 (IL-1) receptor after stimulation. Mice lacking IRAK4 showed severe defects in IL-1 and Toll-like receptor signaling, which established a central role for this family member. The adaptor myeloid differentiation primary response 88 (MyD88) recruits IRAK4, which then phosphorylates IRAK1 on the route to nuclear factor kappa B activation. Emavusertib, listed as CA-4948, and IRAK inhibitor 4 target IRAK4, while IRAK-1-4 Inhibitor I blocks both IRAK1 and IRAK4. The list also contains compounds with other targets, such as the c-Jun N-terminal kinase inhibitor JNK-IN-7.
