14246-71-0Relevant academic research and scientific papers
Selective inhibitors of bacterial t-RNA-(N1G37) methyltransferase (TrmD) that demonstrate novel ordering of the lid domain
Hill, Pamela J.,Abibi, Ayome,Albert, Robert,Andrews, Beth,Gagnon, Moriah M.,Gao, Ning,Grebe, Tyler,Hajec, Laurel I.,Huang, Jian,Livchak, Stephania,Lahiri, Sushmita D.,McKinney, David C.,Thresher, Jason,Wang, Hongming,Olivier, Nelson,Buurman, Ed T.
, p. 7278 - 7288 (2013/10/21)
The tRNA-(N1G37) methyltransferase (TrmD) is essential for growth and highly conserved in both Gram-positive and Gram-negative bacterial pathogens. Additionally, TrmD is very distinct from its human orthologue TRM5 and thus is a suitable target for the design of novel antibacterials. Screening of a collection of compound fragments using Haemophilus influenzae TrmD identified inhibitory, fused thieno-pyrimidones that were competitive with S-adenosylmethionine (SAM), the physiological methyl donor substrate. Guided by X-ray cocrystal structures, fragment 1 was elaborated into a nanomolar inhibitor of a broad range of Gram-negative TrmD isozymes. These compounds demonstrated no activity against representative human SAM utilizing enzymes, PRMT1 and SET7/9. This is the first report of selective, nanomolar inhibitors of TrmD with demonstrated ability to order the TrmD lid in the absence of tRNA.
KINASE MODULATORS AND METHODS OF USE
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Page/Page column 83, (2010/02/15)
The present invention relates to compounds of the Formula I and II wherein R, R21, R25-R33, m, n, X21-X23, and Q1 are defined herein. The compounds modulate protein kinase enzymatic activity to modulate cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinases, particularly p70S6 and/or Akt kinases. Methods of using and preparing the compounds, and pharmaceutical compositions thereof, to treat kinase-dependent diseases and conditions are also an aspect of the invention.
