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 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 vessels supplyi ...

s, such as

sildenafil Sildenafil, sold under the brand name Viagra, among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. It is unclear if it is effective for treating sexual dysfunction in women. It is taken by ...

(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 cycli ...

, selective for the subtypes

PDE5 Cyclic guanosine monophosphate-specific phosphodiesterase type 5 is an enzyme () from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina. It has also been recently discovered to p ...

PDE6 Photoreceptor phosphodiesterase 6 (PDE6 or PDE-6) is a protein complex family, which is highly concentrated in the retina. See also * cGMP * PDE6A * PDE6B * PDE6C * PDE6D * PDE6G Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodieste ...

PDE9 Phosphodiesterase type 9 (PDE9) is a type of phosphodiesterase enzyme. Some inhibitors include BAY 73-6691 BAY 73-6691 is a drug developed by Bayer for the treatment of Alzheimer's disease. It was the first compound developed that acts as a p ...

and PDE11. 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 infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

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 group of protein family, evolution ...

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 aci ...

carrier.

References

Abandoned drugs Phosphodiesterase inhibitors PDE5 inhibitors {{pharma-stub