1403255-88-8

Upstream product

• 771579-27-2 3-(aminomethyl)-4,6-dimethylpyridin-2-ol 
• 1403258-15-0 5-(ethylamino)-4-methyl-4'-(morpholinomethyl)[1,1'-biphenyl]-3-carboxylic acid 
• 1403258-14-9 methyl-5-(ethylamino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxylate 
• 1403258-13-8 5-bromo-3-(ethylamino)-2-methylbenzoic acid methyl ester 
• 1000342-11-9 2-methyl-3-amino-5-bromobenzoic acid methyl ester 
• 79669-49-1 5-bromo-2-methylbenzoic acid 
• 1975-50-4 2-methyl-3-nitrobenzic acid 
• 220514-28-3 5-bromo-2-methyl-3-nitrobenzoic acid methyl ester 
• 107650-20-4 5-bromo-2-methyl-3-nitro-benzoic acid 
• 771579-27-2 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one 

Relevant academic research and scientific papers

Discovery of IHMT-EZH2-115 as a Potent and Selective Enhancer of Zeste Homolog 2 (EZH2) Inhibitor for the Treatment of B-Cell Lymphomas

The enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 that catalyzes methylation of histone H3 lysine 27 (H3K27). Overexpression or mutation of EZH2 has been identified in hematologic malignancies and solid tumors. Based on the structure of EPZ6438 (1) and the binding model with PRC2, we designed a series of analogues aiming to improve the activities of EZH2 mutants. Structure-activity relationship (SAR) exploration at both enzymatic and cellular levels led to the discovery of inhibitor 29. In the biochemical assay, 29 inhibited EZH2 (IC50 = 26.1 nM) with high selectivity over other histone methyltransferases. It was also potent against EZH2 mutants (EZH2 Y641F, IC50 = 72.3 nM). Furthermore, it showed no apparent inhibitory activity against the human ether-á-go-go related gene (hERG) (IC50 > 30 μM). In vivo, 29 exhibited favorable pharmacokinetic properties for oral administration and showed better efficacy than 1 in both Pfeiffer and Karpas-422 cell-mediated xenograft mouse models, indicating that it might be a new potential therapeutic candidate for EZH2 mutant cancers.

Aryl- or Heteroaryl-Substituted Benzene Compounds

The present invention relates to aryl- or heteroaryl-substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.