Work

PBK/TOPK inhibitor OTS964 resistance is mediated by ABCB1-dependent transport function in cancer: in vitro and in vivo study

Year: 2022

Type: article

Abstract: Highlights• ABCB1 overexpression significantly desensitized both drug-selected and gene-transfected cells, which overexpress ABCB1, to OTS964 and that this drug resistance can be antagonized by verapamil, a known ABCB1 inhibitor.Consistently, a similar trend was observed in tumor-bearing mice.• OTS964 stimulated ATPase activity of ABCB1 and upregulated expression levels of ABCB1, resulting in induced resistance to other ABCB1 substrate-drugs, such as paclitaxel.• OTS964 received a comparable affinity score and can dock into the substrate-binding site of human ABCB1 protein.

Source: Molecular Cancer

DOI: 10.1186/s12943-022-01512-0