Zaprinast was an unsuccessful clinical drug candidate that was a precursor to the chemically related

PDE5 inhibitor A phosphodiesterase type 5 inhibitor (PDE5 inhibitor) is a vasodilating medication, drug that works by blocking the degradative action of cGMP-specific phosphodiesterase type 5 (PDE5) on cyclic GMP in the smooth muscle cells lining the blood vess ...

s, such as

sildenafil Sildenafil, sold under the brand name Viagra among others, is a medication used to treat erectile dysfunction and pulmonary hypertension, pulmonary arterial hypertension. It is also sometimes used off-label for the treatment of certain sym ...

(Viagra), which successfully reached the market. It is a

phosphodiesterase inhibitor A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cycl ...

, selective for the subtypes PDE5, PDE6,

PDE9 Phosphodiesterase type 9 (PDE9) is a type of phosphodiesterase enzyme. Some inhibitor Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, ...

and

PDE11 Phosphodiesterase type 11 (PDE11) is a type of phosphodiesterase enzyme. An inhibitor is BC11-38 & Tadalafil Tadalafil, sold under the brand name Cialis among others, is a medication used to treat erectile dysfunction, benign prostatic h ...

. IC₅₀ values are 0.76, 0.15, 29.0, and 12.0 ''μ''M, respectively. Zaprinast inhibits the growth of asexual blood-stage

malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...

parasites ( ''P. falciparum'') ''in vitro'' with an ED₅₀ value of 35 ''μ''M, and inhibits PfPDE1, a '' P. falciparum'' cGMP-specific phosphodiesterase, with an IC₅₀ value of 3.8 ''μ''M. Zaprinast has also been shown to activate the orphan

G-protein coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large protein family, group of evoluti ...

known as

GPR35 G protein-coupled receptor 35 also known as GPR35 is a G protein-coupled receptor which in humans is encoded by the ''GPR35'' gene. Heightened expression of GPR35 is found in immune and gastrointestinal tissues, including the crypts of Lieberküh ...

, both in rats and humans, and to inhibit the mitochondrial

pyruvate Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell. Pyruvic ...

carrier.

References

Abandoned drugs Phosphodiesterase inhibitors PDE5 inhibitors {{pharma-stub