Development of non-peptide ligands of growth factor receptor-bound protein 2-src homology 2 domain using molecular modeling and NMR spectroscopy

Ángel L. Orcajo-Rincón, Silvia Ortega-Gutiérrez, Pedro Serrano, Ivan R. Torrecillas, Kurt Wüthrich, Mercedes Campillo, Leonardo Pardo, Alma Viso, Bellinda Benhamú, María L. López-Rodríguez

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

We report a novel series of non-peptide ligands that inhibit the growth factor receptor-bound protein 2 (Grb2)-Src homology 2 (SH2) domain binding, designed using a combined computational and NMR-driven approach. We have identified a new lead compound, 1n (IC50 = 56 μM), which is cytotoxic in HER2-positive breast cancer cells and disrupts the interaction between HER2 and Grb2. Thus, 1n can be used as a scaffold for the development of efficient Grb2-SH2 domain binding inhibitors. © 2011 American Chemical Society.
Original languageEnglish
Pages (from-to)1096-1100
JournalJournal of Medicinal Chemistry
Volume54
DOIs
Publication statusPublished - 24 Feb 2011

Fingerprint Dive into the research topics of 'Development of non-peptide ligands of growth factor receptor-bound protein 2-src homology 2 domain using molecular modeling and NMR spectroscopy'. Together they form a unique fingerprint.

Cite this