Dbet6

Human colon cancer cell lines (SW48, SW480, SW620, Caco2, HT29, LoVo) and non-transformed colonic epithelial cells (CCD841) were obtained from ATCC and validated as reported^{7 (link),17 (link)}. Chemicals, reagents, and cell culture media were purchased from Invitrogen, dBET6, JQ1 and MZ1 from MedChemExpress, ACE2 shRNA plasmids (#sc-41400-SH) from Santa Cruz Biotechnology, and ACE2 overexpression plasmid with an N-terminal Myc tag (#141185) from Addgene. Plating-densities and cell culture conditions followed the corresponding methodologies for CCK8 cell viability assays, colony formation, cell migration, and FACS-based assessment of apoptosis^{6 (link),7 (link)}, as briefly described below.

Thalidomide (T2524, Tokyo Chemical Industry), pomalidomide (P2074, Tokyo Chemical Industry), lenalidomide (#126-06733, FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan), Thalidomide-O-COOH (HY-103597, MedChemExpress, NJ, USA), CC-122/Avadomide, (HY-100507, MedChemExpress), CC-220/Iberdomide, (HY-101291, MedChemExpress), CC-885 (HY-101488, MedChemExpress), FPFT-2216 (HY-145319, MedChemExpress), biotin-Thalidomide (#913979, Sigma-Aldrich, MA, USA), dBET1 (HY-101838, MedChemExpress), dBET6 (HY-112588, MedChemExpress), ARV-825 (HY-16954, MedChemExpress), MD-224 (HY-114312, MedChemExpress), ARV-110 (HY-138641, MedChemExpress), and MG132 (3175-v, Peptide Institute Inc., Osaka, Japan) were purchased. The procedure and physical data of Thalidomide derivatives and PROTACs synthesised in this study are described in Supplementary Information. All drugs were dissolved in dimethylsulfoxide (DMSO, #045-24511; FUJIFILM Wako Pure Chemical Corporation) at 10–200 mM, stored at −30 °C as stock solutions, and diluted 1,000-fold for in vivo experiments or 100–200-fold for in vitro experiments.