New Potent DOT1L Inhibitors for in Vivo Evaluation in Mouse was written by Stauffer, Frederic;Weiss, Andreas;Scheufler, Clemens;Mobitz, Henrik;Ragot, Christian;Beyer, Kim S.;Calkins, Keith;Guthy, Daniel;Kiffe, Michael;Van Eerdenbrugh, Bernard;Tiedt, Ralph;Gaul, Christoph. And the article was included in ACS Medicinal Chemistry Letters in 2019.Quality Control of 2-Chloropyrimidine-4-carbonitrile This article mentions the following:
In MLL-rearranged cancer cells, disruptor of telomeric silencing 1-like protein (DOT1L) is aberrantly recruited to ectopic loci leading to local hypermethylation of H3K79 and consequently misexpression of leukemogenic genes. A structure-guided optimization of a HTS hit led to the discovery of DOT1L inhibitors with subnanomolar potency, allowing testing of the therapeutic principle of DOT1L inhibition in a preclin. mouse tumor xenograft model. Compounds displaying good exposure in mouse and nanomolar inhibition of target gene expression in cells were obtained and tested in vivo. In the experiment, the researchers used many compounds, for example, 2-Chloropyrimidine-4-carbonitrile (cas: 75833-38-4Quality Control of 2-Chloropyrimidine-4-carbonitrile).
2-Chloropyrimidine-4-carbonitrile (cas: 75833-38-4) belongs to pyrimidine derivatives. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own.Quality Control of 2-Chloropyrimidine-4-carbonitrile
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia