Wang, Shuni; Yang, Hong; Su, Mingbo; Lian, Fulin; Cong, Zhanqing; Wei, Rongrui; Zhou, Yubo; Li, Xingjun; Zheng, Xingling; Li, Chunpu; Fu, Xuhong; Han, Xu; Shi, Qiongyu; Li, Cong; Zhang, Naixia; Geng, Meiyu; Liu, Hong; Li, Jia; Huang, Xun; Wang, Jiang published the artcile< 5-Aminonaphthalene derivatives as selective nonnucleoside nuclear receptor binding SET domain-protein 2 (NSD2) inhibitors for the treatment of multiple myeloma>, Formula: C6H8N2, the main research area is aminonaphthalene sulfonamide preparation NSD2 inhibitor SAR antitumor apoptosis human; 5-Aminonaphthalene derivatives; HTS; Inhibitor; Methyltransferase; Multiple myeloma; NSD2.
Using high-throughput screening (HTS) with biol. analyzes, a series of 5-aminonaphthalene derivatives such as I [X = CO, SO2; R1 = NHCH2Ph, NHPh, NHCH2(4-FC6H4), etc.; R2 = H, NH2, NMe2, etc.] were designed and synthesized as novel NSD2 inhibitors. Among all the prepared compounds, I [R1 = NHCH2Ph, R2 = NH2] displayed a good NSD2 inhibitory activity (IC50 = 2.7μM) and selectivity against both SET-domain-containing and non-SET-domain-containing methyltransferases. Preliminary research indicated the inhibition mechanism of compound I [X = SO2, R1 = NHCH2Ph, R2 = NH2 (II)] by significantly suppressed the methylation of H3K36me2. Compound II specifically inhibited the proliferation of the human B cell precursor leukemia cell line RS4:11 and the human myeloma cell line KMS11 by inducing cell cycle arrest and apoptosis with little cytotoxicity. It was reported that the anti-cancer effect of compound II was partly achieved by completely suppressing the transcriptional activation of NSD2-targeted genes.
European Journal of Medicinal Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 3731-53-1 belongs to class pyridine-derivatives, and the molecular formula is C6H8N2, Formula: C6H8N2.