Description
Chromobox homolog 7 (CBX7) functions through its N-terminal chromodomain, which recognizes histone 3 trimethyl lysine 27 (H3K27me3), to repress gene transcription. It plays a key role in gene transcription in cellular processes related to stem cell self-renewal and differentiation, as well as tumor progression. MS37452 is a competitive inhibitor of CBX7 chromodomain binding to H3K27me3 (K
i = 43 μM). At 250 μM, it has been shown to derepress transcription of the polycomb repressive complex target gene
p16/CDKN2A in prostate cancer cells.
Uses
MS37452 is a competitive inhibitor of CBX7 chromodomain binding to H3K27me3 and has been shown to derepress transcription of the polycomb repressive complex target gene.
Biochem/physiol Actions
MS37452 is a selective Chromobox homolog 7 (CBX7) modulator that disrupts CBX7ChD binding to H3K27me3. MS37452 inhibits CBX7 binding to INK4/ARF gene locus, and induces decline of p14/ARF and p16/INK4a in human PC3 cells.
in vitro
in a previous study, the crystal structures revealed the binding modes of ms37452 and its close analogs that competed against h3k27me3 binding via interactions with key residues in the methyl-lysine binding pocket of cbx7chd. it was further found that ms37452 as the lead compound was able to derepress the transcription of polycomb repressive complex target gene p16/cdkn2a through displacing cbx7 binding to the ink4a/arf locus in prostate cancer cells. these findings showed that ms37452 and its close analogs had the potential to be developed into high-potency chemical modulators targeting cbx7 functions in gene transcription in various disease pathways [1].
References
[1] ren, c. ,morohashi, k.,plotnikov, a.n., et al. small-molecule modulators of methyl-lysine binding for the cbx7 chromodomain. chemistry & biology 22, 161-168 (2015).
