Nat Chem. Biol.
12(12), 1097–1104.
Potent and selective bivalent inhibitors of BET bromodomains.
2016
Waring, M.J., Chen, H., Rabow, A.A., Walker, G., Bobby, R., Boiko, S., Bradbury, R.H., Callis, R., Clark, E., Dale, I., Daniels, D.L., Dulak, A., Flavell, L., Holdgate, G., Jowitt, T.A., Kikhney, A., McAlister, M., Méndez, J., Ogg, D., Patel, J., Petteruti, P., Robb, G.R., Robers, M.B., Saif, S., Stratton, N., Svergun, D.I., Wang, W., Whittaker, D., Wilson, D.M. and Yao, Y.
Notes: The bromodomain and extraterminal (BET) family of proteins contain two bromodomains. A probe compound, biBET, capable of binding both bromodomains of BET proteins in cis is characterized. BDR4-NanoLuc and Halo-tagged histone H3 fusions are used to monitor biBET binding with the NanoBRET Target Engagement system. Interestingly, bivalent binding lead to slower displacement of inhibitor from BDR4 and increased potency. (5078)
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