We continue our series of posts in the Biologics campaign! Today we will focus on Phosphodiesterases (PDEs).

At Chemspace diverse PDEs-related proteins, highly selective antibodies, and kits are available for purchasing!

PDEs are a large family of enzymes that play a significant role in the regulation of cyclic nucleotide (cAMP and cGMP) levels in cells. Nowadays, more than 50 different human PDEs have been identified, which are classified into 11 families. Each of them is characterized by different properties, such as distribution in tissues, sensitivity to inhibitors and co-factors, as well as specificity to the substrate. PDEs are engaged in controlling a wide range of intracellular processes, which makes them attractive targets for drug development associated with various pathologies of the reproduction system, cardiac function, vision, inflammation, cancer development, etc.

Here is a detailed review of various PDEs targeting.

One of the most studied PDEs is the PDE4 subfamily which is reported to participate in the pathogenesis of many inflammatory diseases, e.g., rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), and asthma. The previously approved PDE4 inhibitors, apremilast, and roflumilast, are effective drugs for psoriasis/psoriatic arthritis and COPD. However, the antifibrotic potential of PDE4 inhibitors has not yet been discovered. Recently discovered BI 1015550 is a PDE4 inhibitor showing a preferential enzymatic inhibition of PDE4B. It inhibits lipopolysaccharide-induced TNF-α and phytohemagglutinin-induced interleukin-2 synthesis in human and rat blood cells. Now BI 1015550 is in Phase III clinical trial for the treatment of idiopathic pulmonary fibrosis (IPF) and interstitial lung diseases (ILDs).

More information about the trial evaluation of this drug candidate is here.