MGH-CP1 是TEAD2 (IC50:710 nM) 及TEAD4 (IC50:672 nM) 自棕榈酰化抑制剂，口服有活性，可降低细胞内源性或异位表达的 TEAD 蛋白棕榈酰化水平。MGH-CP1 与 Lats1/2 缺失，是 Myc 的表达受到抑制，阻碍上皮细胞过度增殖，诱导细胞凋亡。

MGH-CP1 is a potent and selective inhibitor TEAD palmitoylation. It exhibits dose-dependent and potent inhibition of TEAD2/4 auto-palmitoylation in vitro with IC50 of 710 nM and 672 nM, respectively.

MGH-CP1 exhibits dose-dependent and potent inhibition of TEAD2/4 auto-palmitoylation in vitro, with IC50 of 710 nM and 672 nM, respectively.?Furthermore, ?MGH-CP1 treatment markedly decreased the palmitoylation levels of endogenous or ectopically expressed TEAD proteins in cells.

MGH-CP1 inhibits TEAD activity in Lats1/2 KO intestine in vivo. MGH-CP1 can effectively inhibit the palmitoylation of TEAD proteins in the intestinal epithelium. MGH-CP1 is well tolerated and has no apparent adverse effect on overall animal health or body weight after 2 weeks of treatment. In contrast to its lack of apparent effect in wild-type intestine, MGH-CP1 treatment effectively inhibits upregulation of the TEAD target genes, CTGF and ANKRD1, in Lats1/2 KO intestine

HEK293T cells, Lats1/2 conditional MEFs and MDA-MB-231 cells were cultured in DMEM supplemented with 10% FBS and 1% penicillin/streptomycin.?For Lats1/2 conditional MEFs carrying CMV-CreER, Lats1/2 was deleted by incubation with 4-OH Tamoxifen (2.5 mM) in DMEM for 4 days prior to further experiment.?Transfection in HEK293T cells was performed using Lipofectamine 2000 (Invitrogen).?For luciferase reporter assays, HEK293T cells were transfected with the luciferase reporter constructs TBS-Luc (8XGTIIC-Luc), Super TOP-FLASH (STF), Gli-BS-Luc, BRE-Luc, and NF-kB-Luc, as well as the expression vectors of pGIPZ-YAP5SA, pGIPZ-YAP6SA, pGIPZ-TAZ4SA, pLV-β-Catenin-ΔN90, pCIG-Wnt3a, pCMV-LRP5C, pCIG-BMP4, pCIG-Gli1,?pGIPZ-IKBKE (Rajurkar et al., 2017) and pCMV-Renilla lucifease.?Luciferase activities were conducted 24 hours after transfection using the dual-luciferase reporter kit (Promega) in the cells treated with or without Wnt3A, LiCl or MGH-CP1.?Assays were conducted in triplicates and quantified using PerkinElmer EnVision plate reader.

896657-58-2

C20H24N4OS

368.5

MGH-CP1

Ethanol:74 mg/mL (200.81 mM)
DMSO:74 mg/mL (200.81 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years