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

doi:10.1021/jm101478n

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

Department of Paediatrics, Obstetrics and Gynaecology, and Preventive Medicine and Public Health

Research output: Contribution to journal › Article › Research › peer-review

8 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 language	English
Pages (from-to)	1096-1100
Journal	Journal of Medicinal Chemistry
Volume	54
DOIs	https://doi.org/10.1021/jm101478n
Publication status	Published - 24 Feb 2011

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10.1021/jm101478n

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Orcajo-Rincón, Á. L., Ortega-Gutiérrez, S., Serrano, P., Torrecillas, I. R., Wüthrich, K., Campillo, M., Pardo, L., Viso, A., Benhamú, B., & López-Rodríguez, M. L. (2011). Development of non-peptide ligands of growth factor receptor-bound protein 2-src homology 2 domain using molecular modeling and NMR spectroscopy. Journal of Medicinal Chemistry, 54, 1096-1100. https://doi.org/10.1021/jm101478n

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

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. {\textcopyright} 2011 American Chemical Society.",

author = "Orcajo-Rinc{\'o}n, {{\'A}ngel L.} and Silvia Ortega-Guti{\'e}rrez and Pedro Serrano and Torrecillas, {Ivan R.} and Kurt W{\"u}thrich and Mercedes Campillo and Leonardo Pardo and Alma Viso and Bellinda Benham{\'u} and L{\'o}pez-Rodr{\'i}guez, {Mar{\'i}a L.}",

year = "2011",

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day = "24",

doi = "10.1021/jm101478n",

language = "English",

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pages = "1096--1100",

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Orcajo-Rincón, ÁL, Ortega-Gutiérrez, S, Serrano, P, Torrecillas, IR, Wüthrich, K, Campillo, M , Pardo, L, Viso, A, Benhamú, B & López-Rodríguez, ML 2011, 'Development of non-peptide ligands of growth factor receptor-bound protein 2-src homology 2 domain using molecular modeling and NMR spectroscopy', Journal of Medicinal Chemistry, vol. 54, pp. 1096-1100. https://doi.org/10.1021/jm101478n

Development of non-peptide ligands of growth factor receptor-bound protein 2-src homology 2 domain using molecular modeling and NMR spectroscopy. / Orcajo-Rincón, Ángel L.; Ortega-Gutiérrez, Silvia; Serrano, Pedro et al.
In: Journal of Medicinal Chemistry, Vol. 54, 24.02.2011, p. 1096-1100.

Research output: Contribution to journal › Article › Research › peer-review

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 -

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

Abstract

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