363597-19-7Relevant academic research and scientific papers
Discovery of an Orally Efficacious MYC Inhibitor for Liver Cancer Using a GNMT-Based High-Throughput Screening System and Structure-Activity Relationship Analysis
Kant, Rajni,Yang, Ming-Hui,Tseng, Chih-Hua,Yen, Chia-Hung,Li, Wei-You,Tyan, Yu-Chang,Chen, Marcelo,Tzeng, Cherng-Chyi,Chen, Wei-Cheng,You, Kaiting,Wang, Wen-Chieh,Chen, Yeh-Long,Chen, Yi-Ming Arthur
, p. 8992 - 9009 (2021/07/19)
Glycine-N-methyl transferase (GNMT) downregulation results in spontaneous hepatocellular carcinoma (HCC). Overexpression of GNMT inhibits the proliferation of liver cancer cell lines and prevents carcinogen-induced HCC, suggesting that GNMT induction is a potential approach for anti-HCC therapy. Herein, we used Huh7 GNMT promoter-driven screening to identify a GNMT inducer. Compound K78 was identified and validated for its induction of GNMT and inhibition of Huh7 cell growth. Subsequently, we employed structure-activity relationship analysis and found a potent GNMT inducer, K117. K117 inhibited Huh7 cell growth in vitro and xenograft in vivo. Oral administration of a dosage of K117 at 10 mpk (milligrams per kilogram) can inhibit Huh7 xenograft in a manner equivalent to the effect of sorafenib at a dosage of 25 mpk. A mechanistic study revealed that K117 is an MYC inhibitor. Ectopic expression of MYC using CMV promoter blocked K117-mediated MYC inhibition and GNMT induction. Overall, K117 is a potential lead compound for HCC- and MYC-dependent cancers.
Synthesis, characterization and crystal structures of 3-hydroxy-N'- [methyl(2-pyridyl)methylene]-2-naphthohydrazide monohydrate and 3-hydroxy-N'-(3,5-dibromo-2-hydroxybenzylidene)-2-naphthohydrazide dimethylformamide solvate
Cheng, Guo-Ping,Xue, Ling-Wei,Yang, Wei-Chun
experimental part, p. 668 - 672 (2012/10/08)
Two hydrazone compounds, 3-hydroxy-N'-[methyl (2-pyridyl)methylene]-2- naphthohydrazide monohydrate (1), and 3-hydroxy-N'-(3,5-dibromo-2- hydroxybenzylidene)-2-naphthohydrazide dimethylformamide solvate (2), have been prepared and characterized by elemental analysis, IR spectra, 1HNMR spectra, and X-ray single crystal structural determination. Compound (1) crystallizes in the monoclinic space group C2/c with unit cell dimensions a = 11.072(2) A, b = 12.017(2) A, c = 23.753(3) A, β = 95.710(2)°, V = 3144.7(9) A3, Z = 8, R1 = 0.0780, and wR2 = 0.1465. Compound (2) crystallizes in the triclinic space group P-1 with unit cell dimensions a = 7.601(2) A, b = 16.522(4) A, c = 17.048(3) A, α = 92.516(11)°, β = 96.726(12)°, γ = 94.117(12)°, V = 2117.8(8) A3, Z = 4, R1 = 0.0490, and wR2 = 0.1012. The hydrazone molecules in the compounds adopt trans configurations about the C=N double bonds. The crystal structures of the compounds are stabilized by intermolecular hydrogen bonds and π ... π stacking interactions. Springer Science+Business Media, LLC 2012.
