Fig. 1: AU-15330, a specific degrader of SWI/SNF ATPases, exhibits preferential cytotoxicity in enhancer-binding transcription factor-driven cancers.
From: Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer
a, Structure of AU-15330 and schematic of SMARCA2, SMARCA4 and PBRM1 domains. AU-15330-targeted bromodomains (BD) are shown. QLQ, conserved Gln, Leu, Gln motif containing domain; HSA, helicase/SANT-associated domain; BRK, Brahma and Kismet domain; SnAC, Snf2 ATP coupling domain; BAH1, bromo-adjacent homology domain 1; BAH2, bromo-adjacent homology domain 2. b, Immunoblots of SMARCA2, SMARCA4 and PBRM1 on treatment of HEK 293 and HeLa cells with AU-15330 at increasing concentrations or time durations. Vinculin is used as a loading control, and is probed on a representative immunoblot. This experiment was repeated independently twice. c, IC50 of AU-15330 in a panel of human-derived cancer or normal cell lines after 5 days of treatment. Known SMARCA4 loss-of-function (LOF) alterations and multiple myeloma (MM) cell lines with MYC rearrangements (MYC-R'ed) are identified below the graph. AR and FOXA1 scores quantify their transcriptional activities using cognate multi-gene signatures.
