– BRD-7586(BRD 7586) is a cell-permeable small molecule inhibitor of SpCas9 with EC50 of 6.2 ??M and 5.7???M in the eGFP-disruption and HiBiT-knock-in assays, respectively. BRD7586 specifically engages SpCas9 but not Cas12a in cells and enhances SpCas9 specificity at multiple loci.