TY - JOUR
T1 - Development of non-peptide ligands of growth factor receptor-bound protein 2-src homology 2 domain using molecular modeling and NMR spectroscopy
AU - Orcajo-Rincón, Ángel L.
AU - Ortega-Gutiérrez, Silvia
AU - Serrano, Pedro
AU - Torrecillas, Ivan R.
AU - Wüthrich, Kurt
AU - Campillo, Mercedes
AU - Pardo, Leonardo
AU - Viso, Alma
AU - Benhamú, Bellinda
AU - López-Rodríguez, María L.
PY - 2011/2/24
Y1 - 2011/2/24
N2 - 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.
AB - 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.
U2 - 10.1021/jm101478n
DO - 10.1021/jm101478n
M3 - Article
SN - 0022-2623
VL - 54
SP - 1096
EP - 1100
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
ER -