A COMPOUND INHIBITS JOINTLY PHOSPHODIESTERASE 1 AND 5
Geng-Long Hsu
Microsurgical Potency Reconstruction and Research Center, 3F 88, Wen-Hu Street Nei-Hu District 114, Taipei, Taiwan
Abstract
XU-1, a bioactive compound with molecular weight 457, was recently isolated from our herbal formula, which we have tested and studied for the past half-decade. An enzyme assay was conducted to explain why XU-1 yields beneficial results but negligible adverse effects. Between April 7th and April 27th, 2017, the activity of compound XU-1 (PT# 1208723) was assayed with methods adhering to standards set by the scientific literature in order to yield results that are both reliable and reproducible. The validity of the results was further ascertained by running reference standards for each assay. IC50 values were calculated using MathIQTM and by a non-linear, least-squares analysis. The observed IC50 values, along with the concentration of radioligand used in the assay, plus the historical values for the dissociation constant (Kd) of the ligand, were used to calculate inhibitor constant (Ki) values; this calculation was based on the Cheng-Prusoff equation (Cheng, Y., Prusoff, W.H., Biochem. Pharmacol. 22:3099-3108, 1973). Finally, the Hill coefficient (nH), which approximates the number of ligand binding sites, was computed with MathIQTM. Hill coefficients that are significantly greater than or less than 1.0 may indicate that the binding displacement interaction does not obey the law of mass action, which would predict a singular binding site. The absence of Standard Error of the Mean (SEM) for any measure indicates that the data were not sufficient for quantifying, and in such cases the values (for Ki, IC50, nH) must be read with an abundance of caution. Excitingly, though, the overall outcome shows that XU-1 enables the inhibition of phosphodiesterase-1, phosphodiesterase-1A, phosphodiesterase-4D2, phosphodiesterase-5, phosphodiesterase-5A, phosphodiesterase-6, phosphodiesterase-9A2 and phosphodiesterase-11A4 enzymes by 82%, 25%, 28%, 91%, 101%, 104%, 25% and 83%, respectively. (Significant results are displayed in rank order of potency for estimated IC50 and/or Ki values). Although phosphodiesterase-5 inhibitors have practically defined the current medical treatment for erectile dysfunction, XU-1 warrants further research because it can significantly inhibit both phosphodiesterase-5 and phosphodiesterase-1, and is the first such agent to have this effect. Our previous studies also suggest that XU-1 may influence the central nervous system in a positive way, including enhancing memory retention. Given these results, we are determined not to overlook the promise and potential of the XU-1 compound.