Ki = 43 μM
MS37452 is a competitive inhibitor of CBX7 chromodomain binding to H3K27me3.
Chromobox homolog 7 (CBX7) functions via its N-terminal chromodomain, which recognizes histone 3 trimethyl lysine 27 (H3K27me3), to repress gene transcription. Chromobox homolog 7 plays a critical role in gene transcription in cellular processes associated with stem cell differentiation and self-renewal, as well as tumor progression.
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].
In vivo: Up to now, there is no animal in vivo data reported.
Clinical trial: So far, no clinical study has been conducted.
Reference:
[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).