Fig. 1: MGH-CP1 and analogues are palmitoylation inhibitors with different outcomes in blocking TEAD–YAP activities.
From: Pharmacological blockade of TEAD–YAP reveals its therapeutic limitation in cancer cells
a Structures of MGH-CP1 and its analogues. b Inhibition of TEAD2 YAP-binding domain (YBD) in vitro autopalmitoylation by MGH-CP compounds. c The MGH-CP12 and MGH-CP34 were docked into MGH-CP1 binding pocket of TEAD2 YAP binding domain. d Cell-based palmitoylation assay using metabolic probe alkyne palmitic acid labeled protein. HEK293A cells were treated with MGH-CP1 and MGH-CP12 separately. e Inhibition of TEAD1/2 and YAP binding in Gal4-TEAD1/2-YAP binding reporter assay by MGH-CP1, 12, 27 and 28 (n = 3 biological repeats). f MGH-CP1 and CP12 inhibit TEAD-binding element–driven luciferase reporter (8xGTIIC-luciferase) (n = 3 biological repeats). g MDA-MB-231 cells were treated with MGH-CP1 and MGH-CP12. Transcriptional levels of Cyr61, CTGF and ANKRD1 were determined using qPCR (n = 3 biological repeats). h Primary and secondary Huh7 tumor spheres treated with MGH-CP1 and MGH-CP12 with indicated concentrations. Dose response curves show MGH-CP1 and MGH-CP12 in Huh7 tumor sphere formation assay (n = 3 biological repeats). i Representative images of HCT116 and HUTU80 cells with knockdown of YAP/TAZ, compared to MGH-CP1 and MGH-CP12 IC50 values, and representative images in 3D tumor cultures with MGH-CP1 and MGH-CP12 treatment in HUTU80 and HCT116 cells. The 3D colonies were measured by diameter at day 4 with compound treatment (n = 51, 53, 59 colonies for control, CP1 and CP12, respectively in HUTU80 cells, n = 52, 58, 66 colonies for control, CP1 and CP12, respectively in HCT116 cells). Scale bar, 50 µm. Data are represented as mean ± S.E.M. P values were determined using two-tailed t-tests. Source data are provided as a Source Data file.
