BRD0539 is a cell-permeable and non-toxic inhibitor of CRISPR-Cas9. BRD0539 inhibits Streptococcus pyogenes Cas9 (SpCas9) (apparent IC50=22 μM) in an in vitro DNA cleavage assay[1].
BRD0539 dose-dependently blocks the formation of the DNA-bound state in a dose-dependent fashion. BRD0539 impairs the perturbation induced by the 4PAM DNA[1].BRD0539 does not interfere with the SpCas9:gRNA interaction[1].BRD0539 is able to inhibit SpCas9 in the eGFP-disruption assay, BRD0539 is unable to inhibit FnCpf1, a structurally different CRISPR-associated nuclease, in the same assay, further highlighting the specificity of BRD0539[1].
[1]. Basudeb Maji, et al. A High-Throughput Platform to Identify Small-Molecule Inhibitors of CRISPR-Cas9. Cell. 2019 May 2;177(4):1067-1079.e19.