8-azaadenosine and 8-chloroadenosine are not selective inhibitors of ADAR.

ABSTRACT: The RNA editing enzyme ADAR, is an attractive therapeutic target for multiple cancers. Through its deaminase activity, ADAR edits adenosine to inosine in dsRNAs. Loss of ADAR in some cancer cell lines causes activation of the type I interferon pathway and the PKR translational repressor, leading to inhibition of proliferation and stimulation of cell death. As such, inhibition of ADAR function is a viable therapeutic strategy for many cancers. However, there are no FDA approved inhibitors of ADAR. Two small molecules have been previously shown to inhibit ADAR or reduce its expression: 8-azaadenosine and 8-chloroadenosine. Here we show that neither molecule is a selective inhibitor of ADAR. Both 8-azaadenosine and 8-chloroadenosine show similar toxicity to ADAR-dependent and independent canc

SUBMITTER: Cottrell KA 

PROVIDER: S-EPMC9113518 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature