1153849-22-9Relevant 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)
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.
NOVEL RHO KINASE INHIBITORS AND METHODS OF USE
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Page/Page column 90, (2012/10/18)
The subject invention concerns materials and methods for treating diseases and disorders associated with expression of Rho associated kinases (ROCKs). Examples of diseases and disorders contemplated within the scope of the invention include, but are not limited to, oncological disorders, cardiovascular diseases, CNS disorders, and inflammatory disorders. In one embodiment, a method of the invention comprises administering a therapeutically effective amount of one or more compounds of the present invention, or a composition comprising the compounds, to a person or animal in need of treatment. The subject invention also concerns compounds that inhibit ROCKs, and compositions that comprise the inhibitor compounds of the invention. Compounds contemplated within the scope of the invention include, but are not limited to, those compounds shown in Table (5).
