Guo, Yinping; Mao, Xin; Xiong, Liang; Xia, Anjie; You, Jing; Lin, Guifeng; Wu, Chengyong; Huang, Luyi; Wang, Yiwei; Yang, Shengyong published the artcile< Structure-Guided Discovery of a Potent and Selective Cell-Active Inhibitor of SETDB1 Tudor Domain>, Synthetic Route of 252932-48-2, the main research area is cell active SETDB1 tudor domain inhibitor structure guided discovery; SETDB1; epigenetics; structure-based optimization; tool compound; tudor domain.
SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferase that promotes the silencing of some tumor suppressor genes and is overexpressed in many cancers. SETDB1 contains a unique tandem tudor domain (TTD) that recognizes histone H3 sequences containing both methylated and acetylated lysines. Beginning with the identification of a hit compound (Cpd1, I), we discovered the first potent and selective small mol. SETDB1-TTD inhibitor (R,R)-59 (II) through stepwise structure-guided optimization. (R,R)-59 showed a KD value of 0.088±0.045μM in the ITC assay. The high potency of (R,R)-59 was well explained by the cocrystal structure of the (R,R)-59-TTD complex. (R,R)-59 is an endogenous binder competitive inhibitor. Evidence has also demonstrated its cellular target engagement. Interestingly, the enantiomer (S,S)-59 did not show activity in all the assays, highlighting the potential of (R,R)-59 as a tool compound in exploring the biol. functions of SETDB1-TTD.
Angewandte Chemie, International Edition published new progress about Antitumor agents. 252932-48-2 belongs to class esters-buliding-blocks, and the molecular formula is C7H10N2O2, Synthetic Route of 252932-48-2.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics