Fragment-based screening of the bromodomain of ATAD2

Harner, Mary J.; Chauder, Brian A.; Phan, Jason; Fesik, Stephen W.

doi:10.1021/jm501035j

Title: Fragment-based screening of the bromodomain of ATAD2

Journal Article · Tue Oct 14 00:00:00 EDT 2014 · Journal of Medicinal Chemistry

DOI:https://doi.org/10.1021/jm501035j· OSTI ID:1346018

Harner, Mary J. ^[1]; Chauder, Brian A. ^[1]; Phan, Jason ^[1]; Fesik, Stephen W. ^[1]

Vanderbilt Univ. School of Medicine, Nashville, TN (United States)

Cellular and genetic evidence suggest that inhibition of ATAD2 could be a useful strategy to treat several types of cancer. To discover small-molecule inhibitors of the bromodomain of ATAD2, we used a fragment-based approach. As a result, fragment hits were identified using NMR spectroscopy, and ATAD2 was crystallized with three of the hits identified in the fragment screen.

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Research Organization:: Vanderbilt Univ. School of Medicine, Nashville, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1346018

Journal Information:: Journal of Medicinal Chemistry, Vol. 57, Issue 22; ISSN 0022-2623

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 61 works

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Cited By (16)

Disulfide bridge formation influences ligand recognition by the ATAD2 bromodomain Gay, Jamie C.; Eckenroth, Brian E.; Evans, Chiara M. Proteins: Structure, Function, and Bioinformatics, Vol. 87, Issue 2 https://doi.org/10.1002/prot.25636	journal	December 2018
ATAD2 in cancer: a pharmacologically challenging but tractable target Hussain, Muzammal; Zhou, Yang; Song, Yu Expert Opinion on Therapeutic Targets, Vol. 22, Issue 1 https://doi.org/10.1080/14728222.2018.1406921	journal	November 2017
Insights Into the Allosteric Inhibition of the SUMO E2 Enzyme Ubc9 Hewitt, William M.; Lountos, George T.; Zlotkowski, Katherine Angewandte Chemie International Edition, Vol. 55, Issue 19 https://doi.org/10.1002/anie.201511351	journal	April 2016
Chemische Epigenetik: der Einfluss chemischer und chemo‐biologischer Techniken auf die Zielstruktur‐Validierung von Bromodomänen Schiedel, Matthias; Moroglu, Mustafa; Ascough, David M. H. Angewandte Chemie, Vol. 131, Issue 50 https://doi.org/10.1002/ange.201812164	journal	November 2019
Overexpression of microRNA‐186 inhibits angiogenesis in retinoblastoma via the Hedgehog signaling pathway by targeting ATAD2 Wu, Shuai; Han, Mei; Zhang, Chao Journal of Cellular Physiology, Vol. 234, Issue 10 https://doi.org/10.1002/jcp.28545	journal	February 2019
Chemical Epigenetics: The Impact of Chemical and Chemical Biology Techniques on Bromodomain Target Validation Schiedel, Matthias; Moroglu, Mustafa; Ascough, David M. H. Angewandte Chemie International Edition, Vol. 58, Issue 50 https://doi.org/10.1002/anie.201812164	journal	December 2019
Bromodomains: a new target class for drug development Cochran, Andrea G.; Conery, Andrew R.; Sims, Robert J. Nature Reviews Drug Discovery, Vol. 18, Issue 8 https://doi.org/10.1038/s41573-019-0030-7	journal	July 2019
Identification of a novel ligand for the ATAD2 bromodomain with selectivity over BRD4 through a fragment growing approach Miller, Duncan C.; Martin, Mathew P.; Adhikari, Santosh Organic & Biomolecular Chemistry, Vol. 16, Issue 11 https://doi.org/10.1039/c8ob00099a	journal	January 2018
Bromodomain biology and drug discovery Zaware, Nilesh; Zhou, Ming-Ming Nature Structural & Molecular Biology, Vol. 26, Issue 10 https://doi.org/10.1038/s41594-019-0309-8	journal	October 2019
The identification of new ATAD2 bromodomain inhibitors: the application of combined ligand and structure-based virtual screening Sepehri, B.; Ghavami, R. SAR and QSAR in Environmental Research, Vol. 28, Issue 12 https://doi.org/10.1080/1062936x.2017.1385532	journal	December 2017
ATAD2 overexpression is associated with progression and prognosis in colorectal cancer Hou, Mingming; Huang, Rui; Song, Yanni Japanese Journal of Clinical Oncology, Vol. 46, Issue 3 https://doi.org/10.1093/jjco/hyv195	journal	January 2016
Observed bromodomain flexibility reveals histone peptide- and small molecule ligand-compatible forms of ATAD2 Poncet-Montange, Guillaume; Zhan, Yanai; Bardenhagen, Jennifer P. Biochemical Journal, Vol. 466, Issue 2 https://doi.org/10.1042/bj20140933	journal	February 2015
Synthesis and Demonstration of the Biological Relevance of sp ³ -rich Scaffolds Distantly Related to Natural Product Frameworks Foley, Daniel J.; Craven, Philip G. E.; Collins, Patrick M. Chemistry - A European Journal, Vol. 23, Issue 60 https://doi.org/10.1002/chem.201704169	journal	October 2017
Insights Into the Allosteric Inhibition of the SUMO E2 Enzyme Ubc9 Hewitt, William M.; Lountos, George T.; Zlotkowski, Katherine Angewandte Chemie, Vol. 128, Issue 19 https://doi.org/10.1002/ange.201511351	journal	April 2016
Disulfide bridge formation influences ligand recognition by the ATAD2 bromodomain Gay, Jamie C.; Eckenroth, Brian E.; Evans, Chiara M. Wiley-Blackwell Publishing, Inc. https://doi.org/10.5167/uzh-162477	text	January 2019
Discovery of I-BRD9, a Selective Cell Active Chemical Probe for Bromodomain Containing Protein 9 Inhibition Theodoulou, Natalie H.; Bamborough, Paul; Bannister, Andrew J. Journal of Medicinal Chemistry, Vol. 59, Issue 4 https://doi.org/10.1021/acs.jmedchem.5b00256	journal	April 2015

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