134701-51-2Relevant articles and documents
THERAPEUTIC COMPOUNDS AND USES THEREOF
-
Page/Page column 96, (2016/08/23)
The present invention relates to compounds of formula (I): and to salts thereof, wherein R1-R6 have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of TAF1. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various TAF1-mediated disorders.
A back-to-front fragment-based drug design search strategy targeting the DFG-out pocket of protein tyrosine kinases
Iwata, Hidehisa,Oki, Hideyuki,Okada, Kengo,Takagi, Terufumi,Tawada, Michiko,Miyazaki, Yasushi,Imamura, Shinichi,Hori, Akira,Lawson, J. David,Hixon, Mark S.,Kimura, Hiroyuki,Miki, Hiroshi
supporting information; experimental part, p. 342 - 346 (2012/06/18)
We present a straightforward process for the discovery of novel back pocket-binding fragment molecules against protein tyrosine kinases. The approach begins by screening against the nonphosphorylated target kinase with subsequent counterscreening of hits against the phosphorylated enzyme. Back pocket-binding fragments are inactive against the phosphorylated kinase. Fragment molecules are of insufficient size to span both regions of the ATP binding pocket; thus, the outcome is binary (back pocket-binding or hinge-binding). Next, fragments with the appropriate binding profile are assayed in combination with a known hinge-binding fragment and subsequently with a known back pocket-binding fragment. Confirmation of back pocket-binding by Yonetani-Theorell plot analysis progresses candidate fragments to crystallization trials. The method is exemplified by a fragment screening campaign against vascular endothelial growth factor receptor 2, and a novel back pocket-binding fragment is presented.
