Preclinical studies showed that its 50% inhibitory concentration (IC50) on Gli1 transcriptional activity was 4.4 nmol/L.450 Similar to LEQ-506, TAK-441 can be used to treat D473H mutants resistant to vismodegib.380 In vivo studies have proved that TAK-441 can inhibit Gli1 mRNA expression and tumor progression in castration resistant PCa and xenotransplantation of pancreatic tumor in mice.451,452 A phase I clinical trial used TAK-441 to treat 34 patients with solid tumors, including colorectal cancer (26%), BCC (21%) and pancreatic cancer (9%). This evidence concerns the gene GLI1 and familial pancreatic carcinoma.