US 12,282,014 B2
Methods of identifying compounds that interfere with ERG-driven misguidance of BAF complexes in TMPRSS2-ERG driven prostate cancers
Cigall Kadoch, Tiburon, CA (US); Gabriel Sandoval, Lemont, IL (US); and William C. Hahn, Newton, MA (US)
Assigned to Dana-Farber Cancer Institute, Inc., Boston, MA (US)
Appl. No. 15/777,428
Filed by Dana-Farber Cancer Institute, Inc., Boston, MA (US)
PCT Filed Nov. 18, 2016, PCT No. PCT/US2016/062911
§ 371(c)(1), (2) Date May 18, 2018,
PCT Pub. No. WO2017/087885, PCT Pub. Date May 26, 2017.
Claims priority of provisional application 62/257,512, filed on Nov. 19, 2015.
Prior Publication US 2018/0328913 A1, Nov. 15, 2018
Int. Cl. G01N 31/00 (2006.01); G01N 33/50 (2006.01); G01N 33/53 (2006.01); G01N 33/574 (2006.01); G01N 33/68 (2006.01)
CPC G01N 33/5011 (2013.01) [G01N 33/57434 (2013.01); G01N 33/6875 (2013.01); G01N 2333/4703 (2013.01); G01N 2500/02 (2013.01)] 6 Claims
 
1. A method of identifying a compound that interferes with the physical interaction between an erythroblast transformation specific (ETS)-related gene (ERG) protein, and a mouse Switch/Sucrose Non-Fermentable (mSWI/SNF) (BRG1-associated factors (BAF)) chromatin remodeling complex protein, wherein
i) the ERG protein is ERG: ΔPNT domain (deletion of pointed domain), ERG: ΔETS domain (deletion of ETS domain), ERG: ΔCAD domain (deletion of C-terminal Activation domain), ERG-Δ225-271, ERG-Δ259-265, or ERG: R367K Mutant (R367K DNA Binding mutant) and
ii) the mSWI/SNF (BAF) chromatin remodeling complex protein is BAF155, the method comprising:
a) administering a candidate compound at a first concentration to a first set of one or more cells;
b) directly determining the strength of the protein-protein interaction between the ERG protein and the mSWI/SNF (BAF) chromatin remodeling complex protein in the first set of one or more cells using mass spectrometry;
c) administering the candidate compound at a second concentration to a second set of one or more cells;
d) directly determining the strength of the protein-protein interaction between the ERG protein and the mSWI/SNF (BAF) chromatin remodeling complex protein in the second set of one or more cells using mass spectrometry; and
e) comparing the strength of the interaction between the ERG protein and the mSWI/SNF (BAF) chromatin remodeling complex protein of the first set of one or more cells to the strength of the interaction between the ERG protein and the mSWI/SNF (BAF) chromatin remodeling complex protein of the second set of one or more cells,
wherein if the strength of the interaction between the ERG protein and the mSWI/SNF (BAF) chromatin remodeling complex protein in the first set of one or more cells is weaker than the strength of the interaction between the ERG protein and the mSWI/SNF (BAF) chromatin remodeling complex protein in the second set of one or more cells, then the candidate compound interferes with interaction between the ERG protein and the mSWI/SNF (BAF) chromatin remodeling complex protein.