Definition

An orally bioavailable, monosodium salt form of R906289, a prodrug of R835, a small molecule inhibitor of interleukin-1 receptor-associated kinases 1 (IRAK1) and 4 (IRAK4), with potential immunomodulating and anti-inflammatory activities. Upon oral administration, R906289 is converted to its active metabolite R835. R835 targets, binds to, and inhibits the activity of IRAK1 and IRAK4. This inhibits lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR4) signaling and LPS/TLR4-induced proinflammatory cytokine production. This may inhibit inflammation and immune-mediated cell destruction in inflammatory and auto-immune diseases where TLR or interleukin 1 receptor (IL-1R) signaling is overactivated. IRAK1 and IRAK4, serine/threonine-protein kinases, play key roles in signaling downstream of TLR and IL-1R, and TLR/IL-1R-induced production of proinflammatory cytokines.