Phosphodiesterase (PDE)

Phosphodiesterases are a diverse family of enzymes that hydrolyse cyclic nucleotides and thus play a key role in regulating intracellular levels of the second messengers cAMP and cGMP, and hence cell function.

ML-030
1013750-77-0
1035572-38-3
LEO29102
1035572-38-3
1038825-85-2
Indimilast
1038825-85-2
106730-54-5
Olprinone
106730-54-5
1082743-70-1
PDE-9 inhibitor
1082743-70-1
1082744-20-4
PF-04447943
1082744-20-4
RGW2938
111786-07-3
1144035-53-9
PF-8380
1144035-53-9
Siguazodan
115344-47-3
1160521-50-5
PDE1-IN-1
1160521-50-5
119615-63-3
119615-63-3
1229652-21-4
HA-130
1229652-21-4
PF 04449613
1236858-52-8
1238697-26-1
TAK-063
1238697-26-1
1239278-59-1
CHF-6001
1239278-59-1

Background


An Overview of Phosphodiesterase (PDE)

Phosphodiesterases (PDE) are a class of enzymes that hydrolyze intracellular second messenger adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). They regulate a variety of signaling and physiological activities within the cell.

Major type of PDE

PDE consist of 11 different families, from PDE1 to PED11. Each family contains different subtypes, each of which has different distribution, expression, regulation, and sensitivity to inhibitors in the cell. PDE1 is one of the earliest discovered PDE isozymes, which hydrolyzes both cAMP and cGMP. There are three subtypes of known PDE1: PDE1A, PDE1B and PDE1C. PDE2 has hydrolysis effects on both cAMP and cGMP, and its bind to cGMP will enhance the ability to hydrolyze cAMP. PDE2 has only one subtype of PDE2A. PDE3 has hydrolysis ability for both cAMP and cGMP, but its hydrolysis ability for cAMP is about ten times greater than that of cGMP. PDE4 is highly specific for cAMP and has four subtypes: PDE4A, PDE4B, PDE4C and PDE4D. PDE 5, 6, and 9 specifically hydrolyze cGMP. PDE 7, and 8 mainly hydrolyze cAMP. PDE10, 11 all contribute to both cAMP and cGMP.

Inhibition of PDE

At present, PDE has become a novel target for drug research. Some PDE inhibitors have been widely used in clinical practice. PDE1 selective inhibitors mainly include nimodipine, vinpocetine, IC86340 and IC224. Studies found that vinpocetine has an anti-inflammatory effect, which can suppress endothelial dysfunction and atherosclerosis, and reducethe risk of stoke. At the same time, vinpocetine also plays a role in suppressing cognitive dysfunction. Currently, the drug has been clinically used to treat neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer disease (AD). PDE3 inhibitors can be used for the treatment of heart failure. And PDE4 inhibitors are used in the treatment of respiratory tract inflammation. While PDE5 inhibitors are used in the treatment of male erectile dysfunction.

PDE and diseases

PDE is involved in the development of various pathological processes such as inflammation, asthma, depression, and erectile dysfunction. The multi-subtype characteristics of PDE have made it attract more and more attention as a new drug target.

Reference:

Giachini F.R., Lima V.V., Carneiro F.S., et al. (2011) Decreased cGMP level contributes to increased contraction in arteries from hypertensive rats. Hypertension, 57( 3): 655-663.