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Gerstenberger BS, Jones H, Knapp S, Marsden B, Nocka K, Owen DR, Philpott M,
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133. Tanaka M, Roberts JM, Seo HS, Souza A, Paulk J, Scott TG, DeAngelo SL, Dhe-Paganon S,
Bradner JE (2016) Design and characterization of bivalent BET inhibitors. Nat Chem Biol
12(12):1089–1096. https://doi.org/10.1038/nchembio.2209
134. Lu J, Qian Y, Altieri M, Dong H, Wang J, Raina K, Hines J, Winkler JD, Crew AP,
Coleman K, Crews CM (2015) Hijacking the E3 ubiquitin ligase cereblon to efficiently target
BRD4. Chem Biol 22(6):755–763. https://doi.org/10.1016/j.chembiol.2015.05.009
135. Zengerle M, Chan K-H, Ciulli A (2015) Selective small molecule induced degradation of the
BET bromodomain protein BRD4. ACS Chem Biol 10(8):1770–1777. https://doi.org/10.
1021/acschembio.5b00216
136. Winter GE, Buckley DL, Paulk J, Roberts JM, Souza A, Dhe-Paganon S, Bradner JE (2015)
Drug development. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science 348(6241):1376–1381. https://doi.org/10.1126/science.aab1433
137. Toure M, Crews CM (2016) Small-molecule PROTACS: new approaches to protein degradation. Angew Chem Int Ed 55(6):1966–1973. https://doi.org/10.1002/anie.201507978
138. Remillard D, Buckley DL, Paulk J, Dastjerdi S, Bradner JE, Brien GL, Armstrong SA,
Sonnett M, Sonnett M, Wuhr M, Seo H-S, Dhe-Paganon S, Wuhr M (2017) Degradation of
336
W. C. K. Pomerantz et al.
Discovery and characterization of small molecule inhibitors of the BET family bromodomains.
J Med Chem 54(11):3827–3838. https://doi.org/10.1021/jm200108t
126. Xinyi H (2003) Fluorescence polarization competition assay: the range of resolvable inhibitor
potency is limited by the affinity of the fluorescent ligand. J Biomol Screen 8(1):34–38. https://
doi.org/10.1177/1087057102239666
127. Cox OB, Krojer T, Collins P, Monteiro O, Talon R, Bradley A, Fedorov O, Amin J, Marsden
BD, Spencer J, von Delft F, Brennan PE (2016) A poised fragment library enables rapid
synthetic expansion yielding the first reported inhibitors of PHIP(2), an atypical bromodomain.
Chem Sci 7(3):2322–2330. https://doi.org/10.1039/C5SC03115J
128. Zhao L, Cao D, Chen T, Wang Y, Miao Z, Xu Y, Chen W, Wang X, Li Y, Du Z, Xiong B, Li J,
Xu C, Zhang N, He J, Shen J (2013) Fragment-based drug discovery of 2-thiazolidinones as
inhibitors of the histone reader BRD4 bromodomain. J Med Chem 56(10):3833–3851. https://
doi.org/10.1021/jm301793a
129. Fish PV, Filippakopoulos P, Bish G, Brennan PE, Bunnage ME, Cook AS, Federov O,
Gerstenberger BS, Jones H, Knapp S, Marsden B, Nocka K, Owen DR, Philpott M,
Picaud S, Primiano MJ, Ralph MJ, Sciammetta N, Trzupek JD (2012) Identification of a
chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization
of a fragment-derived hit. J Med Chem 55(22):9831–9837. https://doi.org/10.1021/
jm3010515
130. Daguer JP, Zambaldo C, Abegg D, Barluenga S, Tallant C, Muller S, Adibekian A,
Winssinger N (2015) Identification of covalent bromodomain binders through DNA display
of small molecules. Angew Chem Int Ed Engl 54(20):6057–6061. https://doi.org/10.1002/
anie.201412276
131. Rhyasen GW, Hattersley MM, Yao Y, Dulak A, Wang W, Petteruti P, Dale IL, Boiko S,
Cheung T, Zhang J, Wen S, Castriotta L, Lawson D, Collins M, Bao L, Ahdesmaki MJ,
Walker G, O’Connor G, Yeh TC, Rabow AA, Dry JR, Reimer C, Lyne P, Mills GB, Fawell
SE, Waring MJ, Zinda M, Clark E, Chen H (2016) AZD5153: a novel bivalent BET
bromodomain inhibitor highly active against hematologic malignancies. Mol Cancer Ther
15(11):2563–2574. https://doi.org/10.1158/1535-7163.mct-16-0141
132. Waring MJ, Chen H, Rabow AA, Walker G, Bobby R, Boiko S, Bradbury RH, Callis R,
Clark E, Dale I, Daniels DL, Dulak A, Flavell L, Holdgate G, Jowitt TA, Kikhney A,
McAlister M, Méndez J, Ogg D, Patel J, Petteruti P, Robb GR, Robers MB, Saif S,
Stratton N, Svergun DI, Wang W, Whittaker D, Wilson DM, Yao Y (2016) Potent and
selective bivalent inhibitors of BET bromodomains. Nat Chem Biol 12:1097. https://doi.org/
10.1038/nchembio.2210. https://www.nature.com/articles/nchembio.2210#supplementaryinformation
133. Tanaka M, Roberts JM, Seo HS, Souza A, Paulk J, Scott TG, DeAngelo SL, Dhe-Paganon S,
Bradner JE (2016) Design and characterization of bivalent BET inhibitors. Nat Chem Biol
12(12):1089–1096. https://doi.org/10.1038/nchembio.2209
134. Lu J, Qian Y, Altieri M, Dong H, Wang J, Raina K, Hines J, Winkler JD, Crew AP,
Coleman K, Crews CM (2015) Hijacking the E3 ubiquitin ligase cereblon to efficiently target
BRD4. Chem Biol 22(6):755–763. https://doi.org/10.1016/j.chembiol.2015.05.009
135. Zengerle M, Chan K-H, Ciulli A (2015) Selective small molecule induced degradation of the
BET bromodomain protein BRD4. ACS Chem Biol 10(8):1770–1777. https://doi.org/10.
1021/acschembio.5b00216
136. Winter GE, Buckley DL, Paulk J, Roberts JM, Souza A, Dhe-Paganon S, Bradner JE (2015)
Drug development. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science 348(6241):1376–1381. https://doi.org/10.1126/science.aab1433
137. Toure M, Crews CM (2016) Small-molecule PROTACS: new approaches to protein degradation. Angew Chem Int Ed 55(6):1966–1973. https://doi.org/10.1002/anie.201507978
138. Remillard D, Buckley DL, Paulk J, Dastjerdi S, Bradner JE, Brien GL, Armstrong SA,
Sonnett M, Sonnett M, Wuhr M, Seo H-S, Dhe-Paganon S, Wuhr M (2017) Degradation of
336
W. C. K. Pomerantz et al.