574729-26-3Relevant articles and documents
Design of Small Molecules That Compete with Nucleotide Binding to an Engineered Oncogenic KRAS Allele
Zhang, Yan,Larraufie, Marie-Hélène,Musavi, Leila,Akkiraju, Hemanth,Brown, Lewis M.,Stockwell, Brent R.
, p. 1380 - 1389 (2018/03/08)
RAS mutations are found in 30% of all human cancers, with KRAS the most frequently mutated among the three RAS isoforms (KRAS, NRAS, and HRAS). However, directly targeting oncogenic KRAS with small molecules in the nucleotide-binding site has been difficult because of the high affinity of KRAS for GDP and GTP. We designed an engineered allele of KRAS and a covalent inhibitor that competes for GTP and GDP. This ligand-receptor combination demonstrates that the high affinity of GTP and GDP for RAS proteins can be overcome with a covalent inhibitor and a suitably engineered binding site. The covalent inhibitor irreversibly modifies the protein at the engineered nucleotide-binding site and is able to compete with GDP and GTP. This provides a new tool for studying KRAS function and suggests strategies for targeting the nucleotide-binding site of oncogenic RAS proteins.
Protein kinase affinity reagents based on a 5-aminoindazole scaffold
Krishnamurty, Ratika,Brock, Amanda M.,Maly, Dustin J.
supporting information; experimental part, p. 550 - 554 (2011/02/27)
Affinity reagents that target protein kinases are powerful tools for signal transduction research. Here, we describe a general set of kinase ligands based on a 5-aminoindazole scaffold. This scaffold can readily be derivatized with diverse binding elements and immobilized analogs allow selective enrichment of protein kinases from complex mixtures.
