Target intelligence / Profile preview

Cyclic GMP Phosphodiesterase (low Km) (cGMP PDE (low Km))

Target
cGMP PDE (low Km)
Molecular classification
Enzyme, Phosphodiesterase
01

Overview

Cyclic GMP phosphodiesterases (cGMP PDEs) are enzymes that hydrolyze cyclic guanosine monophosphate (cGMP) to 5’-GMP, thereby regulating the intracellular levels of cGMP. The "low Km" designation refers to a high affinity for cGMP, meaning these enzymes can efficiently hydrolyze cGMP even at low substrate concentrations. These enzymes regulate key signaling pathways by controlling the breakdown of intracellular second messengers like cAMP and especially cGMP. Several PDE families can hydrolyze cGMP, but those with high affinity (low Km) for cGMP include: PDE1, PDE2, PDE5, and PDE9. Selective inhibitors of certain low Km phosphodiesterase isoforms have clinical applications, such as PDE3 inhibitors in heart failure and PDE5 inhibitors for erectile dysfunction and pulmonary hypertension.

Other names
Low Km cGMP PDEHigh affinity cGMP phosphodiesterase
02

Mechanism of action

Inhibition of cGMP hydrolysis, leading to increased intracellular cGMP levels.

03

Biological functions

Regulation of cGMP levelsSignal transductionVascular tone regulationPlatelet function modulationCardiomyocyte contraction modulation
04

Disease associations

Erectile dysfunctionPulmonary hypertensionHeart failureCardiovascular disease
05

Safety considerations

Potential for drug interactionsSide effects associated with increased cGMP levels
06

Interacting drugs

PDE3 inhibitors

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