Over the past decades, numerous PDE4 inhibitors have been designed and synthesized, among which roflumilast, apremilast, and crisaborole were approved for the treatment of inflammatory airway diseases, psoriatic arthritis, and atopic dermatitis, respectively.

In this review, we illustrate that PDE4 inhibitors retain their therapeutic potential in myriad diseases, but target identification should be more precise to establish selective inhibition of disease-affected PDE4 isoforms while avoiding isoforms involved in adverse effects.

Apr 4, 2013 · Advancements in phosphodiesterase (PDE)-targeted therapies have shown promise in recent years for treating patients with a variety of autoimmune diseases. This review summarizes the development of PDE4 inhibitors and the associated literature with a focus on treatments for autoimmune diseases.

A phosphodiesterase-4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 (PDE4) on cyclic adenosine monophosphate (cAMP). It is a member of the larger family of PDE inhibitors .

In the present study, we rectify this by providing the crystal structures of the catalytic domains of PDE4A, PDE4B and PDE4D in complex with the PDE4 inhibitor NVP {4- [8- (3-nitrophenyl)- [1,7]naphthyridin-6-yl]benzoic acid} as well as the unliganded PDE4C structure.

Jul 20, 2023 · This review provides a comprehensive summary of the development of PDE4 inhibitors in the past few years, along with the structure, clinical and research progress of multiple inhibitors of PDE4, focusing on the research and development strategies of PDE4 inhibitors.

Nov 15, 2005 · In this review we will discuss the cellular and molecular biology of PDE4 isoforms (of which ∼20 have been characterized) and, in particular, the pivotal role that PDE4 isoforms play in achieving compartmentalized signaling in cells by interacting with various scaffold proteins.

Jan 4, 2013 · PDE4 is the main selective cAMP-metabolizing enzyme in inflammatory and immune cells (1, 4). Increases in intracellular cAMP by inhibition of cAMP-degrading PDE4 enzymes reduce most proinflammatory functions of these cells.

Oct 1, 2020 · PDE4 overexpression promotes the progression of neurological disorders like AD, PD, MS, ALS, glioma, stroke, depression etc. PDE4 are mainly expressed in the brain, smooth muscles, cardiovascular tissues and are nearly absent in platelets (Table. 1).

Apr 4, 2013 · Advancements in phosphodiesterase (PDE)-targeted therapies have shown promise in recent years for treating patients with a variety of autoimmune diseases. This review summarizes the development of PDE4 inhibitors and the associated literature with a focus on treatments for autoimmune diseases.