VPC-18005 inhibits ERG-induced transcription and interacts directly with the ERG-ETS domain, and disrupts the ERG binding to DNA. VPC-18005 is a potent inhibitor of luciferase activity[1].
VPC-18005 is found to inhibit pETS-luc reporter activity in PNT1B-ERG and VCaP cells with IC50 values of 3 and 6 μM, respectively[1].VPC-18005 could suppress ERG reporter activity without exhibiting overt cytotoxicity[1].VPC-18005 inhibits migration and invasion of ERG-overexpressing cells in vitro[1].VPC-18005 can antagonize the metastatic potential of ERG-expressing prostate cells[1].The exposure of larvae to 1 or 10 µM of VPC-18005 produced a 20-30% decrease in the dissemination of cancer cells in zebrafsh[2].
[1]. Miriam S Butler, et al. Discovery and characterization of small molecules targeting the DNA-binding ETS domain of ERG in prostate cancer. Oncotarget. 2017 Jun 27;8(26):42438-42454.
[2]. Haneen Amawi, et al. The use of zebrafish model in prostate cancer therapeutic development and discovery. Cancer Chemother Pharmacol. 2021 Mar;87(3):311-325.