EN4, a covalent ligand that targets cysteine 171 (C171) of MYC, is selective for c-MYC over N-MYC and L-MYC. EN4 inhibits MYC transcriptional activity, downregulates MYC targets, and impairs tumorigenesis.
EN4 directly targets MYC in cells, reduces MYC and MAX thermal stability, inhibits MYC transcriptional activity, downregulates multiple MYC transcriptional targets, and impairs tumorigenesis. EN4 treatment significantly impairs 231MFP breast cancer cell proliferation in a dose- and time-dependent manner. EN4 impairs the cell survival of MYC transformed mammary epithelial MCF10A cells, but not parental MCF10A cells that are not dependent on MYC.[1]
EN4 treatment initiated after establishment of a 231MFP breast tumor xenograft in immune-deficient mice also significantly attenuates tumor growth in vivo.[1]
[1] Lydia Boike, et al. Cell Chem Biol. 2021 Jan 21;28(1):4-13.e17.