Effect of potent and selective inhibitors of the Grb2 SH2 domain on cell motilityB Gay
Department of Oncology, Novartis Pharma A G, CH 4002 Basel, Switzerland
J Biol Chem 274:23311-5. 1999
..We demonstrate for the first time a direct role for Grb2 in cell motility and indicate a new avenue for cancer therapeutics...
- Selective GRB2 SH2 inhibitors as anti-Ras therapy
B Gay
Department of Oncology, Novartis Pharmaceuticals Division, Novartis Ltd, Basel, Switzerland
Int J Cancer 83:235-41. 1999
..Moreover, our results demonstrate that, in cells overexpressing receptor tyrosine kinases, such as the EGFR, Grb2 SH2 inhibitors induce expression of the cell cycle inhibitors p21(Waf1/Cip1/CAP1) and p27(Kip1) and reverse transformation...
- Structure-based design and synthesis of high affinity tripeptide ligands of the Grb2-SH2 domain
P Furet
Novartis Pharma Inc, Oncology Research Department, CH 4002 Basel, Switzerland
J Med Chem 41:3442-9. 1998
....
- Discovery of 3-aminobenzyloxycarbonyl as an N-terminal group conferring high affinity to the minimal phosphopeptide sequence recognized by the Grb2-SH2 domain
P Furet
Novartis Pharma Inc, Oncology Research Department, Basel, Switzerland
J Med Chem 40:3551-6. 1997
..The latter confers high affinity (IC50 = 65 nM in an ELISA assay) to the minimal sequence pTyr-Ile-Asn recognized by the Grb2-SH2 domain...
- Structure-based design and synthesis of phosphinate isosteres of phosphotyrosine for incorporation in Grb2-SH2 domain inhibitors. Part 1
P Furet
Novartis Pharmaceuticals, Inc, Therapeutic Area Oncology, Basel, Switzerland
Bioorg Med Chem Lett 10:2337-41. 2000
..The resulting compounds, by exploiting additional interactions, inhibit binding to the Grb2-SH2 domain as potently as the corresponding doubly charged (phosphonomethyl)phenylalanine analogue...
- Structure-based design, synthesis, and X-ray crystallography of a high-affinity antagonist of the Grb2-SH2 domain containing an asparagine mimetic
P Furet
Oncology Research Department, Novartis Pharma Inc, CH 4002 Basel, Switzerland
J Med Chem 42:2358-63. 1999
....
- Mapping the X(+1) binding site of the Grb2-SH2 domain with alpha,alpha-disubstituted cyclic alpha-amino acids
C Garcia-Echeverria
Novartis Pharma Inc, Oncology Research Department, Basel, Switzerland
Bioorg Med Chem Lett 9:2915-20. 1999
..The used of alpha,alpha-disubstituted cyclic alpha-amino acids to map the binding pockets of proteins expands the classical alanine scan concept and takes advantage of the known conformational preferences of these amino acids...
- Convergent synthesis of potent peptide inhibitors of the Grb2-SH2 domain by palladium catalyzed coupling of a terminal alkyne
J Schoepfer
Oncology, Research, Novartis Pharma AG, Basel, Switzerland
Bioorg Med Chem Lett 11:1201-3. 2001
..Using Pd(PPh3)2Cl2 as catalyst, selected naphthyl iodides and triflates were coupled to Ac-Pmp(t-Bu)2-Ac6c-Asn-NH(prop-2-ynyl). The resulting alkyne derivatives were hydrogenated and deprotected to afford potent Grb2-SH2 inhibitors...
ErbB-1 and ErbB-2 acquire distinct signaling properties dependent upon their dimerization partnerM A Olayioye
Friedrich Miescher Institute, CH 4002 Basel, Switzerland
Mol Cell Biol 18:5042-51. 1998
..Differential receptor phosphorylation may, therefore, be the basis for the differences in the signaling properties observed...
