491580-07-5Relevant academic research and scientific papers
5-Aminonaphthalene derivatives as selective nonnucleoside nuclear receptor binding SET domain-protein 2 (NSD2) inhibitors for the treatment of multiple myeloma
Cong, Zhanqing,Fu, Xuhong,Geng, Meiyu,Han, Xu,Huang, Xun,Li, Chunpu,Li, Cong,Li, Jia,Li, Xingjun,Lian, Fulin,Liu, Hong,Shi, Qiongyu,Su, Mingbo,Wang, Jiang,Wang, Shuni,Wei, Rongrui,Yang, Hong,Zhang, Naixia,Zheng, Xingling,Zhou, Yubo
, (2021/06/21)
Approximately 20% of multiple myeloma (MM) are caused by a chromosomal translocation t (4; 14) that leads to the overexpression of the nuclear receptor binding SET domain-protein 2 (NSD2) histone methyltransferase. NSD2 catalyzes the methylation of lysine 36 on histone H3 (H3K36me2) and is associated with transcriptionally active regions. Using high-throughput screening (HTS) with biological analyses, a series of 5-aminonaphthalene derivatives were designed and synthesized as novel NSD2 inhibitors. Among all the prepared compounds, 9c displayed a good NSD2 inhibitory activity (IC50 = 2.7 μM) and selectivity against both SET-domain-containing and non-SET-domain-containing methyltransferases. Preliminary research indicates the inhibition mechanism of compound 9c by significantly suppressed the methylation of H3K36me2. Compound 9c specifically inhibits 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 has been reported that the anti-cancer effect of compound 9c is partly achieved by completely suppressing the transcriptional activation of NSD2-targeted genes. When administered intraperitoneally at 25 mg/kg, compound 9c suppressed the tumor growth of RS4:11 xenografts in vivo and no body weight loss was detected in the tested SCID mice.
SULFONAMIDE DERIVATIVES
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, (2008/06/13)
A medicament for enhancing an effect of a cancer therapy based on a mode of action of DNA injury, which comprises as an active ingredient a compound represented by the general formula (I) or a physiologically acceptable salt thereof: ???wherein R represen
Caffeoyl naphthalenesulfonamide derivatives as HIV integrase inhibitors
Xu, Yu-Wen,Zhao, Gui-Sen,Shin, Cha-Gyun,Zang, Heng-Chang,Lee, Chong-Kyo,Lee, Yong Sup
, p. 3589 - 3593 (2007/10/03)
HIV-1 integrase (IN) is an essential enzyme for retroviral replication and a rational target for the design of anti-AIDS drugs. In the present study, we have designed, synthesized and tested a series of caffeoyl naphthalenesulfonamide derivatives as HIV integrase inhibitors. Among these compounds, we found that HIV integrase inhibitory activities of compounds III-3 and III-4 were more potent than L-chicoric acid (IC50=11.8 μg/mL) and others were comparable to L-chicoric acid. Furthermore, the structure-activity relationships of these compounds were studied. The information gathered from this paper will be useful in the development and design of HIV-1 integrase inhibitors in the future.
