Premium
Discovery of Small Molecules that Bind to K‐Ras and Inhibit Sos‐Mediated Activation
Author(s) -
Sun Qi,
Burke Jason P.,
Phan Jason,
Burns Michael C.,
Olejniczak Edward T.,
Waterson Alex G.,
Lee Taekyu,
Rossanese Olivia W.,
Fesik Stephen W.
Publication year - 2012
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201201358
Subject(s) - gtpase , guanosine , small molecule , guanine nucleotide exchange factor , fragment (logic) , small gtpase , computational biology , chemistry , drug discovery , nucleotide , stereochemistry , biochemistry , combinatorial chemistry , biology , computer science , signal transduction , gene , programming language
Looking for fragments : A fragment‐based screen using NMR spectroscopy was applied to discover ligands that bind to the GTPase K‐Ras and modulate the activity of the nucleotide exchange factor Sos. Structural data on how these fragment‐derived hits bind to the guanosine diphosphate–K‐Ras complex (see picture) provides a starting point for the future discovery of drugs that target K‐Ras activation and signaling.