Discovering Novel P38α Inhibitors for the Treatment of Prostate Cancer Through Virtual Screening Methods

Abstract

<b>Aim:</b> P38α plays a crucial role in the development of castration-resistant prostate cancer. Discovering novel inhibitors of P38α offers potential for the development of new anticancer drugs. <b>Methods & results:</b> Compounds from the Chemdiv and Enamine virtual libraries were filtered to construct the P38α inhibitor-like library. A total of 58 new P38α inhibitors were discovered via virtual screening; these included three compounds (compound 1, 5, 9) with kinase IC₅₀ of below 10 μM. <i>In vitro</i>, these three compounds have the potential to suppress the viabilities of prostate cancer cell lines, however, only compound 9 can inhibit the proliferation and migration of prostate cancer cells. <b>Conclusion:</b> The potent compounds discovered in this study demonstrate anticancer functions by targeting the P38α mitogen-activated protein kinases signaling pathway and are worthy of further investigation.