Discovery of 1,5-diaryl-1,2,4-triazole derivatives as myoferlin inhibitors and their antitumor effects in pancreatic cancer.

<b>Aim:</b> The first inhibitor targeting myoferlin (MYOF), <b>WJ460</b>, bears poor metabolic stability and water solubility. Therefore, this study aimed to improve the drug-like properties of <b>WJ460</b>. <b>Materials &amp; methods:</b> The authors synthesized an array of 1,5-diaryl-1,2,4-triazole analogs and appraised the binding activities with MYOF and their antiproliferative and antimigratory activities against pancreatic cancer cells. <b>Results:</b> Molecular docking and surface plasmon resonance results showed that <b>E4</b> was directly bound to the MYOF-C2D domain. <b>E4</b> effectively inhibited the proliferation and migration of pancreatic cancer cells <i>in vitro</i>. An <i>in silico</i> study suggested that the water solubility of <b>E4</b> was improved by about 22-times than that of <b>WJ460</b>. <b>Conclusion:</b> The findings suggested that the druglike ability of <b>E4</b> was significantly improved.