In silico library screening to find novel anticancer agent with chemosensitizing properties: focus on targeting ataxia telangiectasia and Rad3 related kinase

Abstrakt

To bypass the resistance to conventional chemotherapy, attention is paid to the inhibition of alternative targets such as members of the DNA damage response pathway. In the present study, we performed a three-step virtual screening of potential ATR inhibitors followed by evaluation of antiproliferative and chemosensitizing properties of selected compounds in vitro on a panel of cancer cell lines.

According to pharmacophore resemblance to standard ATR inhibitor VX-970, a total of 17 compounds were purchased and tested. Among those 17 compounds, two proved antiproliferative efficacy in monotherapy, whereas ten compounds were effective in cisplatin co-treatment on the panel of ten different human cell lines.

Klíčová slova

• In silico screening
• drug development
• ATR kinase
• cancer treatment
• chemosensitization