Reference Detail

Ref Type Journal Article
PMID (26819331)
Authors Perlíková P, Rylová G, Nauš P, Elbert T, Tloušťová E, Bourderioux A, Slavětínská LP, Motyka K, Doležal D, Znojek P, Nová A, Harvanová M, Džubák P, Šiller M, Hlaváč J, Hajdúch M, Hocek M
Title 7-(2-Thienyl)-7-Deazaadenosine (AB61), a New Potent Nucleoside Cytostatic with a Complex Mode of Action.
Journal Molecular cancer therapeutics
Vol 15
Issue 5
Date 2016 May
URL
Abstract Text 7-(2-Thienyl)-7-deazaadenosine (AB61) showed nanomolar cytotoxic activities against various cancer cell lines but only mild (micromolar) activities against normal fibroblasts. The selectivity of AB61 was found to be due to inefficient phosphorylation of AB61 in normal fibroblasts. The phosphorylation of AB61 in the leukemic CCRF-CEM cell line proceeds well and it was shown that AB61 is incorporated into both DNA and RNA, preferentially as a ribonucleotide. It was further confirmed that a triphosphate of AB61 is a substrate for both RNA and DNA polymerases in enzymatic assays. Gene expression analysis suggests that AB61 affects DNA damage pathways and protein translation/folding machinery. Indeed, formation of large 53BP1 foci was observed in nuclei of AB61-treated U2OS-GFP-53BP1 cells indicating DNA damage. Random incorporation of AB61 into RNA blocked its translation in an in vitro assay and reduction of reporter protein expression was also observed in mice after 4-hour treatment with AB61. AB61 also significantly reduced tumor volume in mice bearing SK-OV-3, BT-549, and HT-29 xenografts. The results indicate that AB61 is a promising compound with unique mechanism of action and deserves further development as an anticancer agent. Mol Cancer Ther; 15(5); 922-37. ©2016 AACR.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Therapy Description
AB61 AB61 is a 7-deazapurine nucleoside that incorporates into DNA and RNA resulting in DNA/RNA damage thereby repressing protein translation, and is demonstrated to be specifically cytotoxic to cancer cells (PMID: 26819331).
Drug Name Trade Name Synonyms Drug Classes Drug Description
AB61 AB61 is a 7-deazapurine nucleoside that incorporates into DNA and RNA resulting in DNA/RNA damage thereby repressing protein translation, and is demonstrated to be specifically cytotoxic to cancer cells (PMID: 26819331).
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown colorectal cancer not applicable AB61 Preclinical - Cell line xenograft Actionable In a preclinical study, the synthetic nucleoside AB61 demonstrated cytotoxicity in colorectal cancer cell lines in culture and decreased tumor volume and prolonged survival in colorectal cancer cell line xenograft models (PMID: 26819331). 26819331
Unknown unknown breast cancer not applicable AB61 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with the synthetic nucleoside AB61 resulted in repressed protein translation, decreased tumor volume, and prolonged survival in breast cancer cell line xenograft models (PMID: 26819331). 26819331
Unknown unknown ovarian cancer not applicable AB61 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with the synthetic nucleoside AB61 resulted in decreased tumor volume in ovarian cancer cell line xenograft models (PMID: 26819331). 26819331