25539-20-2Relevant academic research and scientific papers
Small-molecule ligands of methyl-lysine binding proteins: Optimization of selectivity for L3MBTL3
James, Lindsey I.,Korboukh, Victoria K.,Krichevsky, Liubov,Baughman, Brandi M.,Herold, J. Martin,Norris, Jacqueline L.,Jin, Jian,Kireev, Dmitri B.,Janzen, William P.,Arrowsmith, Cheryl H.,Frye, Stephen V.
supporting information, p. 7358 - 7371 (2013/10/21)
Lysine methylation is a key epigenetic mark, the dysregulation of which is linked to many diseases. Small-molecule antagonism of methyl-lysine (Kme) binding proteins that recognize such epigenetic marks can improve our understanding of these regulatory mechanisms and potentially validate Kme binding proteins as drug-discovery targets. We previously reported the discovery of 1 (UNC1215), the first potent and selective small-molecule chemical probe of a methyl-lysine reader protein, L3MBTL3, which antagonizes the mono- and dimethyl-lysine reading function of L3MBTL3. The design, synthesis, and structure-activity relationship studies that led to the discovery of 1 are described herein. These efforts established the requirements for potent L3MBTL3 binding and enabled the design of novel antagonists, such as compound 2 (UNC1679), that maintain in vitro and cellular potency with improved selectivity against other MBT-containing proteins. The antagonists described were also found to effectively interact with unlabeled endogenous L3MBTL3 in cells.
Synthesis and cancer cell cytotoxicity of substituted xanthenes
Giri, Rajan,Goodell, John R.,Xing, Chenguo,Benoit, Adam,Kaur, Harneet,Hiasa, Hiroshi,Ferguson, David M.
experimental part, p. 1456 - 1463 (2010/04/29)
A series of substituted xanthenes was synthesized and screened for activity using DU-145, MCF-7, and HeLa cancer cell growth inhibition assays. The most potent compound, 9g ([N,N-diethyl]-9-hydroxy-9-(3-methoxyphenyl)-9H-xanthene-3-carboxamide), was found to inhibit cancer cell growth with IC50 values ranging from 36 to 50 μM across all three cancer cell lines. Structure-activity relationship (SAR) data is presented that indicates additional gains in potency may be realized through further derivatization of the compounds (e.g., the incorporation of a 7-fluoro substituent to 9g). Results are also presented that suggest the compounds function through a unique mechanism of action as compared to that of related acridine and xanthone anticancer agents (which have been shown to intercalate into DNA and inhibit topoisomerase II activity). A structural comparison of these compounds suggests the differences in function may be due to the structure of the xanthene heterocycle which adopts a nonplanar conformation about the pyran ring.
Synthesis and evaluation of acridine- and acridone-based anti-herpes agents with topoisomerase activity
Goodell, John R.,Madhok, Avni A.,Hiasa, Hiroshi,Ferguson, David M.
, p. 5467 - 5480 (2007/10/03)
The discovery of new non-nucleoside antiviral compounds is of significant and growing interest for treating herpes virus infections due to the emergence of nucleoside-resistant strains. Using a whole cell virus-induced cytopathogenic assay, we tested a se
Identification of compounds with anti-West Nile virus activity
Goodell, John R.,Puig-Basagoiti, Francesc,Forshey, Brett M.,Shi, Pei-Yong,Ferguson, David M.
, p. 2127 - 2137 (2007/10/03)
The lack of antiviral compounds targeting flaviviruses represents a significant problem in the development of strategies for treating West Nile Virus (WNV), Dengue, and Yellow Fever infections. Using WNV high-throughput screening techniques developed in o
Substituted xanthones as antimycobacterial agents*, part 1: Synthesis and assignment of 1H/13C NMR chemical shifts
Pickert, Martina,Frahm, August Wilhelm
, p. 177 - 192 (2007/10/03)
A series of substituted xanthones was synthesized in order to prove the hypothesis that electron-withdrawing substituents enhance the antimycobacterial activity of these compounds, which is described by means of a QSAR equation with 13C NMR che
