他达拉非、西地那非和伐地那非对人磷酸二酯酶5A1（PDE5）的生化选择性高于PDE11A4，这表明患者不存在PDE11A4交叉反应。
High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients.
作者信息
Weeks J L, Zoraghi R, Beasley A, Sekhar K R, Francis S H, Corbin J D
机构信息
Department of Molecular Physiology and Biophysics, Vanderbilt University, School of Medicine, Nashville, Tennessee 37232-0615, USA.
出版信息
Int J Impot Res. 2005 Jan-Feb;17(1):5-9. doi: 10.1038/sj.ijir.3901283.
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.
磷酸二酯酶（PDE）11的生理作用尚不清楚，其生化特性也了解甚少。我们已表达了带有组氨酸标签的人PDE11A4，并将该酶纯化至表观均一性。PDE11A4对环磷酸鸟苷（cGMP）的米氏常数（K(m)）为0.97微摩尔，对环磷酸腺苷（cAMP）的米氏常数为2.4微摩尔，cAMP的最大反应速度比对cGMP高4至10倍。鉴于PDE11与PDE5之间的同源性，我们比较了他达拉非（希爱力，礼来-ICOS公司）、伐地那非（艾力达，拜耳-葛兰素史克公司）和西地那非（万艾可，辉瑞公司）对PDE11A4和PDE5A1的生化效力。他达拉非、伐地那非和西地那非对PDE5A1/PDE11A4的选择性分别为40倍、9300倍和1000倍。这表明这三种化合物在患者中均不太可能与PDE11A4发生交叉反应。
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