1073354-96-7Relevant articles and documents
Discovery of Novel Dot1L Inhibitors through a Structure-Based Fragmentation Approach
Chen, Chao,Zhu, Hugh,Stauffer, Frédéric,Caravatti, Giorgio,Vollmer, Susanne,Machauer, Rainer,Holzer, Philipp,M?bitz, Henrik,Scheufler, Clemens,Klumpp, Martin,Tiedt, Ralph,Beyer, Kim S.,Calkins, Keith,Guthy, Daniel,Kiffe, Michael,Zhang, Jeff,Gaul, Christoph
, p. 735 - 740 (2016)
Oncogenic MLL fusion proteins aberrantly recruit Dot1L, a histone methyltransferase, to ectopic loci, leading to local hypermethylation of H3K79 and misexpression of HoxA genes driving MLL-rearranged leukemias. Inhibition of the methyltransferase activity of Dot1L in this setting is predicted to reverse aberrant H3K79 methylation, leading to repression of leukemogenic genes and tumor growth inhibition. In the context of our Dot1L drug discovery program, high-throughput screening led to the identification of 2, a weak Dot1L inhibitor with an unprecedented, induced pocket binding mode. A medicinal chemistry campaign, strongly guided by structure-based consideration and ligand-based morphing, enabled the discovery of 12 and 13, potent, selective, and structurally completely novel Dot1L inhibitors.
COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES
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Page/Page column 165, (2014/06/11)
The present invention provides compounds of formula I: [INSERT FORMULA HERE] or a pharmaceutically acceptable salt, tautomer, or stereoisomer, thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds and methods of using such compounds for treating, preventing, inhibiting, ameliorating, or eradicating the pathology and/or symptomology of a disease caused by a Plasmodium parasite, such as malaria.
Inhibitors of PI3 kinase
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Page/Page column 37-38, (2009/07/10)
The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof, that inhibit phosphoinositide 3-kinase; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds.