zardaverine

Zardaverine is a small molecule, dual-selective phosphodiesterase (PDE) inhibitor targeting PDE3 and PDE4. It was originally developed as a potential bronchodilator and anti-inflammatory agent for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Zardaverine acts by inhibiting PDE3 and PDE4, leading to increased intracellular cAMP levels, which results in bronchodilation, inhibition of inflammatory cell function, and positive inotropic effects on heart muscle. In clinical trials, it showed modest but short-lasting bronchodilatory effects due to rapid elimination from the body. Development for respiratory indications was terminated in 1991 due to these pharmacokinetic limitations. More recently, zardaverine has demonstrated selective antiproliferative activity against certain hepatocellular carcinoma (HCC) cell lines both *in vitro* and *in vivo*; this antitumor effect appears independent of its canonical PDE inhibition mechanism and may involve dysregulation of cell cycle proteins such as Cdk4/6/2, Cyclin A/E, p21, Rb—suggesting potential utility as an anticancer agent[1][5][6][7][8].

Other names

zardaverinaZardaverinum6-(4-(Difluoromethoxy)-3-methoxyphenyl)-3(2H)-pyridazinone