![Author ORCID: We display the ORCID iD icon alongside authors names on our website to acknowledge that the ORCiD has been authenticated when entered by the user. To view the users ORCiD record click the icon. [opens in a new tab]](https://chemrxiv.org/engage/assets/public/chemrxiv/images/logos/orcid.png)
Abstract
A quantitative high throughput screen (qHTS) of 7,988 compounds with annotated libraries using biliary tract cancer cell lines with or without isocitrate dehydrogenase I (IDH1) mutations had identified YC-1 as being selectively cytotoxic against the IDH1 mutant cell lines. We present the structure-activity relationship study of YC-1 analogs and identify the key structural motifs that are essential for activity. We highlight the narrow SAR around the furfuryl alcohol that has been reported as a critical motif that is activated by the sulfotransferase enzyme SULT1A1. Drug-like properties of key analogs are evaluated. We also show the SAR of a smaller subset of 2-choloro-4-amino benzyl alcohols from the NCI compound collection with a similar benzyl alcohol motif. We also demonstrate the ability of key analogs to act as substrates of SULT1A1 in a colorimetric biochemical assay.
