TMDU-3

TMDU-3 is a novel small molecule phosphodiesterase 4 (PDE4) inhibitor developed by Tokyo Medical and Dental University (now part of the Institute of Science Tokyo) in collaboration with RIKEN. Identified via in silico screening as a structural analogue of the PDE4 inhibitor roflumilast, TMDU-3 acts as a cyclic adenosine monophosphate (cAMP) inducer [1.1]. It restores protein kinase A (PKA) activity in white adipose tissue (WAT) to overcome catecholamine resistance caused by obesity. In preclinical models of high-fat diet-induced obesity, oral administration of TMDU-3 restored impaired lipolytic activity and hexosylceramide (HexCer) synthesis, alleviating lipotoxic diseases such as insulin resistance, metabolic dysfunction-associated fatty liver disease (MAFLD), and albuminuria [1.1].