In this manuscript, we have described the extensive SAR studies that were undertaken around YC-1 to define key structural features that were responsible for its selective cytotoxicity towards mIDH1 expressing cells. During our investigation we discovered that the cytotoxicity was dependent on the expression of the sulfotransferase enzyme SULT1A1, independent of mIDH1 status. We proposed that the furfuryl alcohol served as a novel substrate for SULT1A1 and we proposed a mechanism by which the sulfated species can be eliminated, forming a cationic electrophilic species that bioactivates specific proteins whose alkylation leads to the cytotoxicity. Through the development of a biochemical SULT1A1 colorimetric assay, we were able to directly establish YC-1's role as a substrate for this enzyme. We were also able to ascertain the substrate activity of a class of cytotoxic 4-amino benzyl alcohols and prove that they were superior substrates for SULT1A1 in the biochemical assay. We showed that furfuryl amine replacement for the furfuryl alcohol in YC1, while active in cells, may not be turned over by SULT1A1. These studies, in combination with the assessment of drug-like parameters and pharmacokinetics helped us select YC-1 one as a candidate for in vivo evaluation where it showed efficacy in an immunodeficient mouse SULT1A1-expressing tumor xenograft model. While we were able to dose YC-1 at 50 mpk for several days in the xenograft studies without any signs of toxicity detailed investigations are required to establish the specificity of the cytotoxic mechanism and establish a carefully titrated safety window for their therapeutic use.