Technical Articles

PDE4B, a subtype of the phosphodiesterase 4 (PDE4) family, has the core function of specifically hydrolyzing the intracellular second messenger cyclic adenosine monophosphate (cAMP). By regulating cAMP levels, it influences physiological processes such as inflammatory responses and immune activation, making it a key target for inflammatory and neurological diseases. Nerandomilast (BI 1015550), a selective PDE4 inhibitor in the clinical stage, has a clearly defined molecular mechanism of action targeting PDE4B: by binding to the catalytic domain of PDE4B, it competitively inhibits the enzyme's hydrolytic activity toward cAMP, increases intracellular cAMP concentration, subsequently activates the protein kinase A (PKA) signaling pathway, and inhibits the release of pro-inflammatory cytokines (such as IL-6, TNF-α) and the activation of inflammatory cells (such as macrophages, T cells).