A method for the second-site screening of K-Ras in the presence of a covalently attached first-site ligand View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-09

AUTHORS

Qi Sun, Jason Phan, Anders R. Friberg, DeMarco V. Camper, Edward T. Olejniczak, Stephen W. Fesik

ABSTRACT

K-Ras is a well-validated cancer target but is considered to be "undruggable" due to the lack of suitable binding pockets. We previously discovered small molecules that bind weakly to K-Ras but wanted to improve their binding affinities by identifying ligands that bind near our initial hits that we could link together. Here we describe an approach for identifying second site ligands that uses a cysteine residue to covalently attach a compound for tight binding to the first site pocket followed by a fragment screen for binding to a second site. This approach could be very useful for targeting Ras and other challenging drug targets. More... »

PAGES

11-14

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10858-014-9849-8

DOI

http://dx.doi.org/10.1007/s10858-014-9849-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023383452

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25087006


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