ND-2158

**ND-2158** is a potent and selective small molecule inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4), with a Ki of 1.3 nM, developed using structure-based drug design as described in patent WO2013106535. It competitively binds the ATP pocket of IRAK4, disrupting MYD88-dependent signaling pathways activated by Toll-like receptors (TLRs) and interleukin-1 receptors, thereby inhibiting NF-κB and STAT3 activation, proinflammatory cytokine production (e.g., TNFα, IL-6, IL-1β), and downstream effects like cell proliferation and migration. Preclinical studies demonstrated efficacy in models of autoimmune diseases (rheumatoid arthritis, gout), lymphoid malignancies (chronic lymphocytic leukemia [CLL], activated B-cell diffuse large B-cell lymphoma [ABC-DLBCL] with MYD88 mutations), and other inflammatory conditions, with good oral bioavailability and synergy with BTK or Syk inhibitors.[1][2][3][7][8]

Other names

(2S)-2-hydroxy-3-[(3R)-12-{[(1r,4r)-4-(morpholin-4-yl)cyclohexyl]oxy}-7-thia-9,11-diazatricyclo[6.4.0.0²,⁶]dodeca-1(12),2(6),8,10-tetraen-3-yl]propanamide