MMSL 2024, 93(1):68-83 | DOI: 10.31482/mmsl.2023.009

IN SILICO LIBRARY SCREENING TO FIND NOVEL ANTICANCER AGENT WITH CHEMOSENSITIZING PROPERTIES: FOCUS ON TARGETING ATAXIA TELANGIECTASIA AND Rad3 RELATED KINASEOriginal article

Darina Muthna ORCID...1, Tomas Kucera ORCID...2, Zbynek Vecera2, Lukas Gorecki ORCID...3, Martin Andrs ORCID...3, Martina Rezacova ORCID...1*, Jan Korabecny ORCID...3*
1 Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 38 Hradec Kralove, Czech Republic
2 Department of Toxicology and Military Pharmacy, Trebesska 1575, 500 05 Hradec Kralove, Czech Republic
3 Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic

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.

Keywords: In silico screening; drug development; ATR kinase; cancer treatment; chemosensitization

Received: January 24, 2023; Revised: February 16, 2023; Accepted: February 16, 2023; Prepublished online: March 1, 2023; Published: March 1, 2024  Show citation

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Muthna, D., Kucera, T., Vecera, Z., Gorecki, L., Andrs, M., Rezacova, M., & Korabecny, J. (2024). IN SILICO LIBRARY SCREENING TO FIND NOVEL ANTICANCER AGENT WITH CHEMOSENSITIZING PROPERTIES: FOCUS ON TARGETING ATAXIA TELANGIECTASIA AND Rad3 RELATED KINASE. MMSL, 93(1), 68-83. doi: 10.31482/mmsl.2023.009
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