Discovering novel P38α inhibitors for the treatment of prostate cancer through virtual screening methods.

Aim: P38 alpha plays a crucial role in the development of castration-resistant prostate cancer. Discovering novel inhibitors of P38 alpha offers potential for the development of new anticancer drugs. Methods & results: Compounds from the Chemdiv and Enamine virtual libraries were filtered to construct the P38 alpha inhibitor-like library. A total of 58 new P38 alpha inhibitors were discovered via virtual screening; these included three compounds (compound 1, 5, 9) with kinase IC50 of below 10 mu M. In vitro, 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. Conclusion: The potent compounds discovered in this study demonstrate anticancer functions by targeting the P38 alpha mitogen-activated protein kinases signaling pathway and are worthy of further investigation.