Abstract
The physiological role of phosphodiesterase (PDE)11 is unknown and its biochemical characteristics are poorly understood. We have expressed human His-tagged PDE11A4 and purified the enzyme to apparent homogeneity. PDE11A4 displays K(m) values of 0.97 microM for cGMP and 2.4 microM for cAMP, and maximal velocities were 4- to 10-fold higher for cAMP than for cGMP. Given the homology between PDE11 and PDE5, we have compared the biochemical potencies of tadalafil (Cialis, Lilly-ICOS), vardenafil (Levitra, Bayer-GSK), and sildenafil (Viagra, Pfizer Inc.) for PDE11A4 and PDE5A1. PDE5A1/PDE11A4 selectivities are 40-, 9300-, and 1000-fold for tadalafil, vardenafil, and sildenafil, respectively. This suggests that none of these three compounds is likely to crossreact with PDE11A4 in patients.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3',5'-Cyclic-GMP Phosphodiesterases
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Carbolines / pharmacology*
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Cross Reactions
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Cyclic AMP / metabolism
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Cyclic GMP / metabolism
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Cyclic Nucleotide Phosphodiesterases, Type 5
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DNA, Complementary / biosynthesis
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DNA, Complementary / genetics
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Humans
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Imidazoles / pharmacology*
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Kinetics
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Phosphodiesterase Inhibitors / pharmacology*
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Phosphoric Diester Hydrolases / metabolism*
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Piperazines / pharmacology*
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Purines
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Recombinant Proteins
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Sildenafil Citrate
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Substrate Specificity
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Sulfones / pharmacology*
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Tadalafil
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Triazines / pharmacology*
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Vardenafil Dihydrochloride
Substances
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Carbolines
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DNA, Complementary
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Imidazoles
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Phosphodiesterase Inhibitors
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Piperazines
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Purines
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Recombinant Proteins
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Sulfones
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Triazines
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Vardenafil Dihydrochloride
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Tadalafil
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Sildenafil Citrate
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Cyclic AMP
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Phosphoric Diester Hydrolases
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3',5'-Cyclic-GMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 5
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PDE11A protein, human
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PDE5A protein, human
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Cyclic GMP