YH-0623 is an orally active inhibitor of mitochondrial RNA polymerase (POLRMT) with an IC50 of 50.48 nM as determined by NanoBRET assay. It exhibits antiproliferative effects on 22Rv1 cells by downregulating mitochondrial gene expression. YH-0623 suppresses 22Rv1 cell growth, colony formation, and expression of proteins related to OXPHOS. Significant tumor growth inhibition was observed in a prostate cancer xenograft mouse model. YH-0623 is applicable for prostate cancer research.