Featured Publications


Phthalimide Conjugation as a Strategy for in vivo Target Protein Degradation (Science, 2015) 

Small-molecule antagonists disable discrete biochemical functions of protein targets. For multi- domain proteins, the consequence of traditional drug action is limited to disruption of domain- specific activity. This short-coming challenges the development of effective inhibitors of multi- domain scaffold proteins, notably transcription factors. We therefore devised a chemical strategy to prompt ligand-dependent target protein degradation via phthalimide conjugation, thereby hijacking the Cereblon E3 ubiquitin ligase complex. We appended a competitive antagonist of BET bromodomains with phthalimide-conjugates that induce immediate and highly selective Cereblon-dependent BET protein degradation, leading to improved and accelerated anti-leukemic efficacy in vitro and in vivo. The reach of this approach is illustrated by a second series of probes that degrade the cytosolic protein, FKBP12. Together, these findings identify a general, all- chemical strategy to control target protein stability, with implications for approaching previously intractable protein targets. 

For a .pdf of the manuscript click HERE.


Genome-wide localization of small molecules (Nature Biotechnology, 2014)

A vast number of small-molecule ligands, including therapeutic drugs under development and in clinical use, elicit their effects by binding specific proteins associated with the genome. An ability to map the direct interactions of a chemical entity with chromatin genome-wide could provide important insights into chemical perturbation of cellular function. Here we describe a method that couples ligand-affinity capture and massively parallel DNA sequencing (Chem-seq) to identify the sites bound by small chemical molecules throughout the human genome. 

 


Discovery and Characterization of Super-Enhancer-Associated Dependencies in Diffuse Large B Cell Lymphoma (Cancer Cell, 2013)

Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. 

 


Small-Molecule Inhibition of BRDT for Male Contraception (Cell, 2012)

Here, we report potent inhibition of the testis-specific member BRDT, which is essential for chromatin remodeling during spermatogenesis. Biochemical and crystallographic studies confirm that occupancy of the BRDT acetyl-lysine binding pocket by JQ1 prevents recognition of acetylated histone H4. Treatment of mice with JQ1 reduced seminiferous tubule area, testis size, and spermatozoa number and motility without affecting hormone levels. Although JQ1-treated males mate normally, inhibitory effects of JQ1 evident at the spermatocyte and round spermatid stages cause a complete and reversible contraceptive effect. 


BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc (Cell, 2011)

MYC contributes to the pathogenesis of a majority of human cancers, yet strategies to modulate the function of the c-Myc oncoprotein do not exist. Toward this objective, we have targeted MYC transcription by interfering with chromatin-dependent signal transduction to RNA polymerase, specifically by inhibiting the acetyl-lysine recognition domains (bromodomains) of putative coactivator proteins implicated in transcriptional initiation and elongation. Using a selective small-molecule bromodomain inhibitor, JQ1, we identify BET bromodomain proteins as regulatory factors for c-Myc. BET inhibition by JQ1 downregulates MYC transcription, followed by genome-wide downregulation of Myc-dependent target genes. In experimental models of multiple myeloma, a Myc- dependent hematologic malignancy, JQ1 produces a potent antiproliferative effect associated with cell- cycle arrest and cellular senescence. 


Selective inhibition of BET bromodomains (Nature, 2010)

Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. 


Selected Publications (of > 120)

Cancer: An essential passenger with p53.
Bradner JE
Nature 2015

Selective Inhibition of HDAC1 and HDAC2 as a Potential Therapeutic Option for B-ALL.
Stubbs MC, Kim W, Bariteau M, Davis T, Vempati S, Minehart J, Witkin M, Qi J, Krivtsov AV, Bradner JE, Kung AL, Armstrong SA
Clin. Cancer Res. 2015

Comparative pharmacokinetic properties and antitumor activity of the marine HDACi Largazole and Largazole peptide isostere.
Pilon JL, Clausen DJ, Hansen RJ, Lunghofer PJ, Charles B, Rose BJ, Thamm DH, Gustafson DL, Bradner JE, Williams RM
Cancer Chemother. Pharmacol. 2015

MLL partial tandem duplication leukemia cells are sensitive to small molecule DOT1L inhibition.
Khn MW, Hadler MJ, Daigle SR, Koche RP, Krivtsov AV, Olhava EJ, Caligiuri MA, Huang G, Bradner JE, Pollock RM, Armstrong SA
Haematologica 2015

Correction: Regulation of MYC Expression and Differential JQ1 Sensitivity in Cancer Cells.
Fowler T, Ghatak P, Price DH, Conaway R, Conaway J, Chiang CM, Bradner JE, Shilatifard A, Roy AL
PLoS ONE 2015

Chromatin proteomic profiling reveals novel proteins associated with histone-marked genomic regions.
Ji X, Dadon DB, Abraham BJ, Lee TI, Jaenisch R, Bradner JE, Young RA
Proc. Natl. Acad. Sci. U.S.A. 2015

Acetylation site specificities of lysine deacetylase inhibitors in human cells.
Schlz C, Weinert BT, Wagner SA, Beli P, Miyake Y, Qi J, Jensen LJ, Streicher W, McCarthy AR, Westwood NJ, Lain S, Cox J, Matthias P, Mann M, Bradner JE, Choudhary C
Nat. Biotechnol. 2015

Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies.
Chan SC, Selth LA, Li Y, Nyquist MD, Miao L, Bradner JE, Raj GV, Tilley WD, Dehm SM
Nucleic Acids Res. 2015

Therapeutic targeting of BET bromodomain protein, Brd4, delays cyst growth in ADPKD.
Zhou X, Fan LX, Peters DJ, Trudel M, Bradner JE, Li X
Hum. Mol. Genet. 2015

The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models.
Garcia PL, Miller AL, Kreitzburg KM, Council LN, Gamblin TL, Christein JD, Heslin MJ, Arnoletti JP, Richardson JH, Chen D, Hanna CA, Cramer SL, Yang ES, Qi J, Bradner JE, Yoon KJ
Oncogene 2015

Selective inhibition of protein arginine methyltransferase 5 blocks initiation and maintenance of B-cell transformation.
Alinari L, Mahasenan KV, Yan F, Karkhanis V, Chung JH, Smith EM, Quinion C, Smith PL, Kim L, Patton JT, Lapalombella R, Yu B, Wu Y, Roy S, De Leo A, Pileri S, Agostinelli C, Ayers L, Bradner JE, Chen-Kiang S, Elemento O, Motiwala T, Majumder S, Byrd JC, Jacob S, Sif S, Li C, Baiocchi RA
Blood 2015

Convergence of developmental and oncogenic signaling pathways at transcriptional super-enhancers.
Hnisz D, Schuijers J, Lin CY, Weintraub AS, Abraham BJ, Lee TI, Bradner JE, Young RA
Mol. Cell 2015

DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia.
Chen CW, Koche RP, Sinha AU, Deshpande AJ, Zhu N, Eng R, Doench JG, Xu H, Chu SH, Qi J, Wang X, Delaney C, Bernt KM, Root DE, Hahn WC, Bradner JE, Armstrong SA
Nat. Med. 2015

The SWI/SNF ATPases are Required for Triple Negative Breast Cancer Cell Proliferation.
Wu Q, Madany P, Akech J, Dobson JR, Douthwright S, Browne G, Colby JL, Winter GE, Bradner JE, Pratap J, Sluder G, Bhargava R, Chiosea S, van Wijnen AJ, Stein JL, Stein GS, Lian JB, Nickerson JA, Imbalzano AN
J. Cell. Physiol. 2015

Structure-guided DOT1L probe optimization by label-free ligand displacement.
Yi JS, Federation AJ, Qi J, Dhe-Paganon S, Hadler M, Xu X, St Pierre R, Varca AC, Wu L, Marineau JJ, Smith WB, Souza A, Chory EJ, Armstrong SA, Bradner JE
ACS Chem. Biol. 2015

Therapeutic strategies to inhibit MYC.
McKeown MR, Bradner JE
Cold Spring Harb Perspect Med 2014

Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation.
Lane AA, Chapuy B, Lin CY, Tivey T, Li H, Townsend EC, van Bodegom D, Day TA, Wu SC, Liu H, Yoda A, Alexe G, Schinzel AC, Sullivan TJ, Malinge S, Taylor JE, Stegmaier K, Jaffe JD, Bustin M, te Kronnie G, Izraeli S, Harris MH, Stevenson KE, Neuberg D, Silverman LB, Sallan SE, Bradner JE, Hahn WC, Crispino JD, Pellman D, Weinstock DM
Nat. Genet. 2014

Regulation of MYC expression and differential JQ1 sensitivity in cancer cells.
Fowler T, Ghatak P, Price DH, Conaway R, Conaway J, Chiang CM, Bradner JE, Shilatifard A, Roy AL
PLoS ONE 2014

Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma.
Vogl DT, Stadtmauer EA, Tan KS, Heitjan DF, Davis LE, Pontiggia L, Rangwala R, Piao S, Chang YC, Scott EC, Paul TM, Nichols CW, Porter DL, Kaplan J, Mallon G, Bradner JE, Amaravadi RK
Autophagy 2014

A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia.
Grschel S, Sanders MA, Hoogenboezem R, de Wit E, Bouwman BA, Erpelinck C, van der Velden VH, Havermans M, Avellino R, van Lom K, Rombouts EJ, van Duin M, Dhner K, Beverloo HB, Bradner JE, Dhner H, Lwenberg B, Valk PJ, Bindels EM, de Laat W, Delwel R
Cell 2014

An in-tumor genetic screen reveals that the BET bromodomain protein, BRD4, is a potential therapeutic target in ovarian carcinoma.
Baratta MG, Schinzel AC, Zwang Y, Bandopadhayay P, Bowman-Colin C, Kutt J, Curtis J, Piao H, Wong LC, Kung AL, Beroukhim R, Bradner JE, Drapkin R, Hahn WC, Liu JF, Livingston DM
Proc. Natl. Acad. Sci. U.S.A. 2014

Identification of ATR-Chk1 pathway inhibitors that selectively target p53-deficient cells without directly suppressing ATR catalytic activity.
Kawasumi M, Bradner JE, Tolliday N, Thibodeau R, Sloan H, Brummond KM, Nghiem P
Cancer Res. 2014

NF-KB directs dynamic super enhancer formation in inflammation and atherogenesis.
Brown JD, Lin CY, Duan Q, Griffin G, Federation AJ, Paranal RM, Bair S, Newton G, Lichtman AH, Kung AL, Yang T, Wang H, Luscinskas FW, Croce KJ, Bradner JE, Plutzky J
Mol. Cell 2014

Targeting STAT5 in hematologic malignancies through inhibition of the bromodomain and extra-terminal (BET) bromodomain protein BRD2.
Liu S, Walker SR, Nelson EA, Cerulli R, Xiang M, Toniolo PA, Qi J, Stone RM, Wadleigh M, Bradner JE, Frank DA
Mol. Cancer Ther. 2014

Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells.
Fiskus W, Sharma S, Qi J, Valenta JA, Schaub LJ, Shah B, Peth K, Portier BP, Rodriguez M, Devaraj SG, Zhan M, Sheng J, Iyer SP, Bradner JE, Bhalla KN
Mol. Cancer Ther. 2014

Syntheses and discovery of a novel class of cinnamic hydroxamates as histone deacetylase inhibitors by multimodality molecular imaging in living subjects.
Chan CT, Qi J, Smith W, Paranol R, Mazitschek R, West N, Reeves R, Chiosis G, Schreiber SL, Bradner JE, Paulmurugan R, Gambhir SS
Cancer Res. 2014

MLL3 is a haploinsufficient 7q tumor suppressor in acute myeloid leukemia.
Chen C, Liu Y, Rappaport AR, Kitzing T, Schultz N, Zhao Z, Shroff AS, Dickins RA, Vakoc CR, Bradner JE, Stock W, LeBeau MM, Shannon KM, Kogan S, Zuber J, Lowe SW
Cancer Cell 2014

Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia.
Gutierrez A, Pan L, Groen RW, Baleydier F, Kentsis A, Marineau J, Grebliunaite R, Kozakewich E, Reed C, Pflumio F, Poglio S, Uzan B, Clemons P, VerPlank L, An F, Burbank J, Norton S, Tolliday N, Steen H, Weng AP, Yuan H, Bradner JE, Mitsiades C, Look AT, Aster JC
J. Clin. Invest. 2014

Improved targeting of JAK2 leads to increased therapeutic efficacy in myeloproliferative neoplasms.
Bhagwat N, Koppikar P, Keller M, Marubayashi S, Shank K, Rampal R, Qi J, Kleppe M, Patel HJ, Shah SK, Taldone T, Bradner JE, Chiosis G, Levine RL
Blood 2014

Convergent transcription at intragenic super-enhancers targets AID-initiated genomic instability.
Meng FL, Du Z, Federation A, Hu J, Wang Q, Kieffer-Kwon KR, Meyers RM, Amor C, Wasserman CR, Neuberg D, Casellas R, Nussenzweig MC, Bradner JE, Liu XS, Alt FW
Cell 2014

From transcriptional regulation to drugging the cancer epigenome.
Bradner JE
Genome Med 2014

RapidCaP, a novel GEM model for metastatic prostate cancer analysis and therapy, reveals myc as a driver of Pten-mutant metastasis.
Cho H, Herzka T, Zheng W, Qi J, Wilkinson JE, Bradner JE, Robinson BD, Castillo-Martin M, Cordon-Cardo C, Trotman LC
Cancer Discov 2014

Selective inhibition of BET bromodomain epigenetic signalling interferes with the bone-associated tumour vicious cycle.
Lamoureux F, Baud'huin M, Rodriguez Calleja L, Jacques C, Berreur M, Rdini F, Lecanda F, Bradner JE, Heymann D, Ory B
Nat Commun 2014

Biased multicomponent reactions to develop novel bromodomain inhibitors.
McKeown MR, Shaw DL, Fu H, Liu S, Xu X, Marineau JJ, Huang Y, Zhang X, Buckley DL, Kadam A, Zhang Z, Blacklow SC, Qi J, Zhang W, Bradner JE
J. Med. Chem. 2014

Inhibition of bromodomain proteins for the treatment of human diffuse large B-cell lymphoma.
Trabucco SE, Gerstein RM, Evens AM, Bradner JE, Shultz LD, Greiner DL, Zhang H
Clin. Cancer Res. 2014

Activation of SOX2 expression by BRD4-NUT oncogenic fusion drives neoplastic transformation in NUT midline carcinoma.
Wang R, Liu W, Helfer CM, Bradner JE, Hornick JL, Janicki SM, French CA, You J
Cancer Res. 2014

Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition.
Tang Y, Gholamin S, Schubert S, Willardson MI, Lee A, Bandopadhayay P, Bergthold G, Masoud S, Nguyen B, Vue N, Balansay B, Yu F, Oh S, Woo P, Chen S, Ponnuswami A, Monje M, Atwood SX, Whitson RJ, Mitra S, Cheshier SH, Qi J, Beroukhim R, Tang JY, Wechsler-Reya R, Oro AE, Link BA, Bradner JE, Cho YJ
Nat. Med. 2014

7,9-Diaryl-1,6,8-trioxaspiro[4.5]dec-3-en-2-ones: readily accessible and highly potent anticancer compounds.
D'Erasmo MP, Smith WB, Munoz A, Mohandas P, Au AS, Marineau JJ, Quadri LE, Bradner JE, Murelli RP
Bioorg. Med. Chem. Lett. 2014

Repression of BIM mediates survival signaling by MYC and AKT in high-risk T-cell acute lymphoblastic leukemia.
Reynolds C, Roderick JE, LaBelle JL, Bird G, Mathieu R, Bodaar K, Colon D, Pyati U, Stevenson KE, Qi J, Harris M, Silverman LB, Sallan SE, Bradner JE, Neuberg DS, Look AT, Walensky LD, Kelliher MA, Gutierrez A
Leukemia 2014

AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes.
Deshpande AJ, Deshpande A, Sinha AU, Chen L, Chang J, Cihan A, Fazio M, Chen CW, Zhu N, Koche R, Dzhekieva L, Ibez G, Dias S, Banka D, Krivtsov A, Luo M, Roeder RG, Bradner JE, Bernt KM, Armstrong SA
Cancer Cell 2014

Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma.
Lee DH, Qi J, Bradner JE, Said JW, Doan NB, Forscher C, Yang H, Koeffler HP
Int. J. Cancer 2014

c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells.
Roderick JE, Tesell J, Shultz LD, Brehm MA, Greiner DL, Harris MH, Silverman LB, Sallan SE, Gutierrez A, Look AT, Qi J, Bradner JE, Kelliher MA
Blood 2014

Notch inhibition allows oncogene-independent generation of iPS cells.
Ichida JK, TCW J, T C W J, Williams LA, Carter AC, Shi Y, Moura MT, Ziller M, Singh S, Amabile G, Bock C, Umezawa A, Rubin LL, Bradner JE, Akutsu H, Meissner A, Eggan K
Nat. Chem. Biol. 2014

An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia.
Knoechel B, Roderick JE, Williamson KE, Zhu J, Lohr JG, Cotton MJ, Gillespie SM, Fernandez D, Ku M, Wang H, Piccioni F, Silver SJ, Jain M, Pearson D, Kluk MJ, Ott CJ, Shultz LD, Brehm MA, Greiner DL, Gutierrez A, Stegmaier K, Kung AL, Root DE, Bradner JE, Aster JC, Kelliher MA, Bernstein BE
Nat. Genet. 2014

BET protein antagonist JQ1 is synergistically lethal with FLT3 tyrosine kinase inhibitor (TKI) and overcomes resistance to FLT3-TKI in AML cells expressing FLT-ITD.
Fiskus W, Sharma S, Qi J, Shah B, Devaraj SG, Leveque C, Portier BP, Iyer S, Bradner JE, Bhalla KN
Mol. Cancer Ther. 2014

Pre-clinical analysis of changes in intra-cellular biochemistry of glioblastoma multiforme (GBM) cells due to c-Myc silencing.
Rajagopalan V, Vaidyanathan M, Janardhanam VA, Bradner JE
Cell. Mol. Neurobiol. 2014

Quantitative ChIP-Seq normalization reveals global modulation of the epigenome.
Orlando DA, Chen MW, Brown VE, Solanki S, Choi YJ, Olson ER, Fritz CC, Bradner JE, Guenther MG
Cell Rep 2014

PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains.
Picaud S, Da Costa D, Thanasopoulou A, Filippakopoulos P, Fish PV, Philpott M, Fedorov O, Brennan P, Bunnage ME, Owen DR, Bradner JE, Taniere P, O'Sullivan B, Mller S, Schwaller J, Stankovic T, Knapp S
Cancer Res. 2013

BCL2-specific inhibitor ABT-199 synergizes strongly with cytarabine against the early immature LOUCY cell line but not more-differentiated T-ALL cell lines.
Anderson NM, Harrold I, Mansour MR, Sanda T, McKeown M, Nagykary N, Bradner JE, Lan Zhang G, Look AT, Feng H
Leukemia 2013

A cyclodextrin-capped histone deacetylase inhibitor.
Amin J, Puglisi A, Clarke J, Milton J, Wang M, Paranal RM, Bradner JE, Spencer J
Bioorg. Med. Chem. Lett. 2013

The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins.
Lu G, Middleton RE, Sun H, Naniong M, Ott CJ, Mitsiades CS, Wong KK, Bradner JE, Kaelin WG
Science 2013

Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex.
Gao C, Dimitrov T, Yong KJ, Tatetsu H, Jeong HW, Luo HR, Bradner JE, Tenen DG, Chai L
Blood 2013

Genome-wide localization of small molecules.
Anders L, Guenther MG, Qi J, Fan ZP, Marineau JJ, Rahl PB, Lovn J, Sigova AA, Smith WB, Lee TI, Bradner JE, Young RA
Nat. Biotechnol. 2013

BET acetyl-lysine binding proteins control pathological cardiac hypertrophy.
Spiltoir JI, Stratton MS, Cavasin MA, Demos-Davies K, Reid BG, Qi J, Bradner JE, McKinsey TA
J. Mol. Cell. Cardiol. 2013

MYC, a downstream target of BRD-NUT, is necessary and sufficient for the blockade of differentiation in NUT midline carcinoma.
Grayson AR, Walsh EM, Cameron MJ, Godec J, Ashworth T, Ambrose JM, Aserlind AB, Wang H, Evan GI, Kluk MJ, Bradner JE, Aster JC, French CA
Oncogene 2013

Bromodomain and extraterminal (BET) protein inhibition suppresses human T cell leukemia virus 1 (HTLV-1) Tax protein-mediated tumorigenesis by inhibiting nuclear factor B (NF-B) signaling.
Wu X, Qi J, Bradner JE, Xiao G, Chen LF
J. Biol. Chem. 2013

BET bromodomain inhibition of MYC-amplified medulloblastoma.
Bandopadhayay P, Bergthold G, Nguyen B, Schubert S, Gholamin S, Tang Y, Bolin S, Schumacher SE, Zeid R, Masoud S, Yu F, Vue N, Gibson WJ, Paolella BR, Mitra SS, Cheshier SH, Qi J, Liu KW, Wechsler-Reya R, Weiss WA, Swartling FJ, Kieran MW, Bradner JE, Beroukhim R, Cho YJ
Clin. Cancer Res. 2013

The use of small molecules in somatic-cell reprogramming.
Federation AJ, Bradner JE, Meissner A
Trends Cell Biol. 2013

Synthesis and HDAC inhibitory activity of isosteric thiazoline-oxazole largazole analogs.
Guerra-Bubb JM, Bowers AA, Smith WB, Paranal R, Estiu G, Wiest O, Bradner JE, Williams RM
Bioorg. Med. Chem. Lett. 2013

The bromodomain protein Brd4 insulates chromatin from DNA damage signalling.
Floyd SR, Pacold ME, Huang Q, Clarke SM, Lam FC, Cannell IG, Bryson BD, Rameseder J, Lee MJ, Blake EJ, Fydrych A, Ho R, Greenberger BA, Chen GC, Maffa A, Del Rosario AM, Root DE, Carpenter AE, Hahn WC, Sabatini DM, Chen CC, White FM, Bradner JE, Yaffe MB
Nature 2013

Recruitment of Brd4 to the human papillomavirus type 16 DNA replication complex is essential for replication of viral DNA.
Wang X, Helfer CM, Pancholi N, Bradner JE, You J
J. Virol. 2013

Targeting MYCN in neuroblastoma by BET bromodomain inhibition.
Puissant A, Frumm SM, Alexe G, Bassil CF, Qi J, Chanthery YH, Nekritz EA, Zeid R, Gustafson WC, Greninger P, Garnett MJ, McDermott U, Benes CH, Kung AL, Weiss WA, Bradner JE, Stegmaier K
Cancer Discov 2013

Selective HDAC1/HDAC2 Inhibitors Induce Neuroblastoma Differentiation.
Stacey M. Frumm, Zi Peng Fan, Kenneth N. Ross, Jeremy R. Duvall, Supriya Gupta, Lynn VerPlank, Byung-Chul Suh, Edward Holson, Florence F. Wagner, William B. Smith, Ronald M. Paranal, Christopher F. Bassil, Jun Qi, Giovanni Roti, Andrew L. Kung, James E. Bradner, Nicola Tolliday, Kimberly Stegmaier
Chemistry & Biology (23 May 2013, Vol. 20, Issue 5, pp. 713-725)

Efficacy of BET bromodomain inhibition in Kras-mutant non-small cell lung cancer.
Shimamura T, Chen Z, Soucheray M, Carretero J, Kikuchi E, Tchaicha JH, Gao Y, Cheng KA, Cohoon TJ, Qi J, Akbay E, Kimmelman AC, Kung AL, Bradner JE, Wong KK
Clin. Cancer Res. 2013

Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins.
Lockwood WW, Zejnullahu K, Bradner JE, Varmus H
Proc. Natl. Acad. Sci. U.S.A. 2012

C-terminal binding protein-2 regulates response of epithelial ovarian cancer cells to histone deacetylase inhibitors.
Barroilhet L, Yang J, Hasselblatt K, Paranal RM, Ng SK, Rauh-Hain JA, Welch WR, Bradner JE, Berkowitz RS, Ng SW
Oncogene 2012

Clinicopathologic features and long-term outcomes of NUT midline carcinoma.
Bauer DE, Mitchell CM, Strait KM, Lathan CS, Stelow EB, Ler SC, Muhammed S, Evans AG, Sholl LM, Rosai J, Giraldi E, Oakley RP, Rodriguez-Galindo C, London WB, Sallan SE, Bradner JE, French CA
Clin. Cancer Res. 2012

BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism.
Boehm D, Calvanese V, Dar RD, Xing S, Schroeder S, Martins L, Aull K, Li PC, Planelles V, Bradner JE, Zhou MM, Siliciano RF, Weinberger L, Verdin E, Ott M
Cell Cycle 2012

BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia.
Ott CJ, Kopp N, Bird L, Paranal RM, Qi J, Bowman T, Rodig SJ, Kung AL, Bradner JE, Weinstock DM
Blood 2012

Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition.
Weigert O, Lane AA, Bird L, Kopp N, Chapuy B, van Bodegom D, Toms AV, Marubayashi S, Christie AL, McKeown M, Paranal RM, Bradner JE, Yoda A, Gaul C, Vangrevelinghe E, Romanet V, Murakami M, Tiedt R, Ebel N, Evrot E, De Pover A, Rgnier CH, Erdmann D, Hofmann F, Eck MJ, Sallan SE, Levine RL, Kung AL, Baffert F, Radimerski T, Weinstock DM
J. Exp. Med. 2012

Transcriptional Amplification in Tumor Cells with Elevated c-Myc
Charles Y. Lin, Jakob Loven, Peter B. Rahl, Ronald M. Paranal, Christopher B. Burge, James E. Bradner, Tong Ihn Lee, and Richard A. Young*
*Corresponding authors. Cell. 26 August 2012; In press.

Small-molecule inhibition of BRDT for male contraception
Matzuk MM, McKeown MR, Filippakopoulos P, Li Q, Ma L, Ango JE, Lemieux ME, Picaud S, Yu RN, Qi J, Knapp S, Bradner JE.

*Corresponding authors. Cell. 17 August 2012; In press.

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BET bromodomain inhibition targets both c-MYC and IL7R in high-risk acute lymphoblastic leukemia
Christopher J. Ott, Nadja Kopp, Liat Bird, Ronald M. Paranal, Jun Qi, Teresa Bowman, Scott J. Rodig, Andrew L. Kung, James E. Bradner and David M. Weinstock.

*Corresponding Authors. Blood. 2012 Aug 17. [Epub ahead of print]

Preclinical activity, pharmacodynamic and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma.
Santo L, Hideshima T, Kung AL, Tseng JC, Tamang D, Yang M, Jarpe M, van Duzer JH, Mazitschek R, Ogier WC, Cirstea D, Rodig S, Eda H, Scullen T, Canavese M,Bradner, J. E., Anderson KC, Jones SS, Raje N.
Blood. 2012 Jan 19. [Epub ahead of print]

BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc.
Delmore, J. E., Issa, G. C., Lemieux, M. E., Rahl, P. B., Shi, J., Jacobs, H. M., Kastritis, E., Gilpatrick, T., Paranal, R. M., Qi, J., Chesi, M., Schinzel, A. C., McKeown, M. R., Heffernan, T. P., Vakoc, C. R., Bergsagel, P. L., Ghobrial, I. M., Richardson, P. G., Young, R. A., Hahn, W. C., Anderson, K. C., Kung, A. L., Bradner, J. E., Mitsiades, C. S.
Cell. 2011 Sep 16;146(6):904-17. Epub 2011 Sep 1. *Corresponding authors


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RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia .
Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, Magoon D, Qi J, Blatt K, Wunderlich M, Taylor MJ, Johns C, Chicas A, Mulloy JC, Kogan SC, Brown P, Valent P, Bradner JE , Lowe SW, Vakoc CR.
Nature. 2011 Aug 3. doi: 10.1038/nature10334. [Epub ahead of print]

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Differentiation of NUT Midline Carcinoma in Humans and Mice by Epigenomic Reprogramming


Schwartz, B. E., Hofer, M. D., Lemieux, M. E., Bauer, D. E., Cameron, M. J., West, N. H., Agoston, E. S., Reynoird, N., Khochbin, S., Ince, T. A., Christie, A., Janeway, K. A., Vargas, S. O., Perez-Atayde, A. R., Aster, J. C., Sallan, S. E., Kung, A. L., Bradner, J. E. , French, C. A.
Cancer Research - Published OnlineFirst March 31, 2011;

Selective inhibition of BET bromodomains.
Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, McKeown MR, Wang Y, Christie AL, West N, Cameron MJ, Schwartz B, Heightman TD, La Thangue N, French CA, Wiest O, Kung AL, Knapp S* and Bradner JE*.
Nature. 2010 Sep 24 [Epub ahead of print]; 468:1067-73 *Corresponding authors

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HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans.
Marubayashi S, Koppikar P, Taldone T, Abdel-Wahab O, West N, Bhagwat N, Caldas-Lopes E, Ross KN, Gonen M, Gozman A, Ahn JH, Rodina A, Ouerfelli O, Yang G, Hedvat C, Bradner JE, Chiosis G, Levine RL*.
J Clin Invest. 2010 Sep 13. pii: 42442. *Corresponding authors
As featured in SciBX. 2010 Sept 30; doi:10.1038/scibx.2010.1138.

Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease.
Bradner JE, Mak R, Tanguturi SK, Mazitschek R, Haggarty SJ, Ross K, Chang CY, Bosco J, West N, Morse E, Lin K, Shen JP, Kwiatkowski NP, Gheldof N, Dekker J, DeAngelo DJ, Carr SA, Schreiber SL, Golub TR, Ebert BL.
Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12617-22. Epub 2010 Jun 28.

Chemical phylogenetics of histone deacetylases.
Bradner JE, West N, Grachan ML, Greenberg EF, Haggarty SJ, Warnow T and Mazitschek R.
Nature Chemical Biology. 2010 Feb 7; Advance online publication. *Corresponding authors

Direct inhibition of the NOTCH transcription factor complex.
Moellering RE, Cornejo M, Davis TN, Del Bianco C, Aster JC, Blacklow SC, Kung AL, Gilliland DG, Verdine GL and Bradner JE.
Nature. 2009 Nov 12; 462: 182-188.
As featured in Nature. 2009 Nov 12; 462:171-172.
As featured in Chemical & Engineering News. 2009 Nov 16; 87(46):9.
As featured in Science Signaling. 2009 Nov 17; 2:ec369.
As featured in Developmental Cell. 2009 Dec 15; 17(6):750-2.
As featured in ACS Chemical Biology. 2009 Dec 18; 4(12):975-8.

Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease.
McCarroll SA, Bradner JE, Turpeinen H, Volin L, Martin PJ, Chilewski SD, Antin JH, Lee SJ, Ruutu T, Storer B, Warren EH, Zhang B, Zhao LP, Ginsburg D, Soiffer RJ, Partanen J, Hansen JA, Ritz J, Palotie A and Altshuler D.
Nature Genetics. 22 November 2009; 41(12):1341-4.
As featured in Nature Genetics. 2009 41:1263-4.

HDAC2 negatively regulates memory formation and synaptic plasticity.
Guan JS, Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, Gao J, Nieland TJ, Zhou Y, Wang X, Mazitschek R, Bradner JE, DePinho RA, Jaenisch R, Tsai LH.
Nature. 2009; 459(7243):55-60.

A pulse at the heart of targeted therapy
Bradner JE
Nature Chemical Biology. 2009;5(3):144-5.

Identification and characterization of small molecule inhibitors of a class I histone deacetylase from Plasmodium falciparum.
Patel V, Mazitschek R, Coleman B, Nguyen C, Urgaonkar S, Cortese J, Barker RH, Greenberg E, Tang W, Bradner JE, Schreiber SL, Duraisingh MT, Wirth DF, Clardy J.
Journal of Medicinal Chemistry. 2009;52(8):2185-7.

Synthesis and HDAC Inhibitory Activity of Largazole Analogs: Alteration of the Zinc-Binding Domain and Macrocyclic Scaffold.
Bowers A, West N, Newkirk TL, Troutman-Youngman AE, Schreiber SL, Bradner JE and Williams RM.

Organic Letters. 2009;11(6):1301-4.

Synthesis and Conformation-Activity Relationships of the Peptide Isosteres of FK228 and Largazole.
Bowers A, Greshock TJ, West N, Estiu G, Schreiber SL, Wiest O, Williams RM and Bradner JE.

Journal of the American Chemical Society. 2009 Feb 4.

The Total Synthesis and Biological Mode of Action of Largazole: A Potent Class I Histone Deacetylase (HDAC) Inhibitor.
Bowers A, West N, Taunton J, Schreiber SL, Bradner JE and Williams RM.

Journal of the American Chemical Society. 2008 Aug 20;130(33):11219-22. Epub 2008 Jul 19.

On the Structural Origin of Selectivity in Class II-Selective Histone Deacetylase Inhibitors.
Estiu G, Greenberg EF, Harrison CB, Mazitschek R, Bradner JE and Wiest O.

Journal of Medicinal Chemistry. 2008;51(10):2898-906.

Coactivation of Receptor Tyrosine Kinases Affects the Response of Tumor Cells to Targeted Therapies.
Stommel JM, Kimmelman AC, Ying H, Nabioullin R, Ponugoti AH, Wiedemeyer R, Stegh AH, Bradner JE, Ligon KL, Brennan C, Chin L, Depinho RA.
Science. 2007;318(5848):287-90.

Fluorous-Based Small-Molecule Microarrays for the Discovery of Histone Deacetylase Inhibitors.
Vegas AJ, Bradner JE, Tang W, McPherson OM, Greenberg EF, Koehler AN, Schreiber SL.

Angewandte Chemie. 2007;46(42):7960-4.
As featured in Angew Chem Int Ed Engl. 2008;47:2-5.

A Method for the Covalent Capture and Screening of Diverse Small Molecules in a Microarray Format.
Bradner JE, McPherson OM, Koehler AN.
Nature Protocols. 2006;1(5):2344-52.

A robust small-molecule microarray platform for screening cell lysates.
Bradner JE, McPherson OM, Mazitschek R, Barnes-Seeman D, Shen JP, Dhaliwal J, Stevenson KE, Duffner JL, Park SB, Neuberg DS, Nghiem P, Schreiber SL, Koehler AN.
Chemistry & Biology. 2006;13(5):493-504.
As featured in Nature Biotechnology 2006; 24: 799.

Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma.
Hideshima T, Bradner JE, Wong J, Chauhan D, Richardson P, Schreiber SL, Anderson KC.

Proceedings of the National Academy of Sciences 2005; 102: 8567-72.

DNA-bend modulation in a repressor-to-activator switching mechanism.
Ansari AZ, Bradner JE and O'Halloran TV
Nature. 374:371-375, 1995.