An inhibitor of Bcl-2 family proteins induces regression of solid tumours
- T. Oltersdorf, S. Elmore, S. Rosenberg
- 2 June 2005
Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation.
ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor.
- C. Tse, A. Shoemaker, S. Elmore
- Biology, MedicineCancer Research
- 1 May 2008
The biological properties and rationale for clinical trials evaluating ABT-263 in small-cell lung cancer and B-cell malignancies are provided and the oral efficacy should provide dosing flexibility to maximize clinical utility both as a single agent and in combination regimens are reported.
Structure of Bcl-xL-Bak Peptide Complex: Recognition Between Regulators of Apoptosis
- M. Sattler, H. Liang, S. Fesik
- Chemistry, BiologyScience
- 14 February 1997
The structure and binding affinities of mutant Bak peptides indicate that the Bak peptide adopts an amphipathic α helix that interacts with Bcl-xL through hydrophobic and electrostatic interactions.
Drugging the undruggable RAS: Mission Possible?
- A. Cox, S. Fesik, A. Kimmelman, Ji Luo, C. Der
- BiologyNature reviews. Drug discovery
- 17 October 2014
This Review summarizes the progress and the promise of five key approaches for the development of RAS-inhibitory molecules and addresses the issue of whether blocking RAS membrane association is a viable approach.
X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death
- S. Muchmore, M. Sattler, S. Fesik
- Biology, ChemistryNature
- 23 May 1996
The arrangement of the α-helices in Bcl-xL is reminiscent of the membrane translocation domain of bacterial toxins, in particular diphia toxin and the colicins, and may provide a clue to the mechanism of action of the B cl-2 family of proteins.
14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation.
- S. R. Datta, A. Katsov, M. Greenberg
- BiologyMolecules and Cells
- 1 July 2000
Structural biology of the Bcl-2 family of proteins.
- A. Petros, E. Olejniczak, S. Fesik
- BiologyBiochimica et Biophysica Acta
- 1 March 2004
Discovering High-Affinity Ligands for Proteins: SAR by NMR
- S. B. Shuker, P. Hajduk, R. Meadows, S. Fesik
- Chemistry, BiologyScience
- 29 November 1996
A nuclear magnetic resonance (NMR)-based method is described in which small organic molecules that bind to proximal subsites of a protein are identified, optimized, and linked together to produce high-affinity ligands and appears particularly useful in target-directed drug research.
Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain
- Zhihong Liu, Chaohong Sun, S. Fesik
- Chemistry, BiologyNature
- 21 December 2000
The solution structure of the BIR3 domain of X-linked IAP (XIAP) complexed with a functionally active nine-residue peptide derived from the N terminus of Smac is determined and should aid in the design of small molecules that may be used for the treatment of cancers that overexpress IAPs.
Structural Basis for the Inhibition of Caspase-3 by XIAP
- S. Riedl, M. Renatus, G. Salvesen
- Chemistry, BiologyCell
- 9 March 2001