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High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients

International Journal of Impotence Research volume 17, pages 5–9 (2005)Cite this article

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 Km values of 0.97 μM for cGMP and 2.4 μM 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.

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Acknowledgements

We thank Drs Jun Kotera and Kenji Omori of Tanabe Seiyaku Co., Ltd (Saitama, Japan) for the generous gifts of PDE11A3/A4 polyclonal antibody as well as the cDNA encoding human PDE11A4. We also thank Bayer Inc. for kindly providing purified vardenafil (Levitra™, Bayer-GSK). This work was supported by NIH Grants DK58277 and DK40029, NIH Training Grant 5T32HL07752, and AHA Postdoctoral Grant 032525B.

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  1. Department of Molecular Physiology and Biophysics, Vanderbilt University, School of Medicine, Nashville, Tennessee, USA

    J L Weeks II, R Zoraghi, A Beasley, S H Francis & J D Corbin

  2. Vanderbilt Center for Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    K R Sekhar

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  1. J L Weeks II
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  2. R Zoraghi
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Correspondence to J D Corbin.

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Weeks, J., Zoraghi, R., Beasley, A. et al. High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients. Int J Impot Res 17, 5–9 (2005). https://doi.org/10.1038/sj.ijir.3901283

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