Journal article

Discovery of a novel allosteric inhibitor scaffold for polyadenosine-diphosphate-ribose polymerase 14 (PARP14) macrodomain 2

Abstract:: The polyadenosine-diphosphate-ribose polymerase 14 (PARP14) has been implicated in DNA damage response pathways for homologous recombination. PARP14 contains three (ADP ribose binding) macrodomains (MD) whose exact contribution to overall PARP14 function in pathology remains unclear. A medium throughput screen led to the identification of N-(2(-9H-carbazol-1-yl)phenyl)acetamide (GeA-69, 1) as a novel allosteric PARP14 MD2 (second MD of PARP14) inhibitor. We herein report medicinal chemistry around this novel chemotype to afford a sub-micromolar PARP14 MD2 inhibitor. This chemical series provides a novel starting point for further development of PARP14 chemical probes.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Moustakim, M., Riedel, K., Schuller, M., Gehring, A., Monteiro, O., Martin, S., Fedorov, O., Heer, J., Dixon, D., Elkins, J., Knapp, S., Bracher, F., & Brennan, P. (2018). Discovery of a novel allosteric inhibitor scaffold for polyadenosine-diphosphate-ribose polymerase 14 (PARP14) macrodomain 2. Bioorganic and Medicinal Chemistry, 26(11), 2965–2972.

MLA Style

Moustakim, M., et al. “Discovery of a Novel Allosteric Inhibitor Scaffold for Polyadenosine-Diphosphate-Ribose Polymerase 14 (PARP14) Macrodomain 2.” Bioorganic and Medicinal Chemistry, vol. 26, no. 11, Elsevier, 2018, pp. 2965–72.

Chicago Style

Moustakim, M, K Riedel, M Schuller, A Gehring, O Monteiro, S Martin, O Fedorov, et al. 2018. “Discovery of a Novel Allosteric Inhibitor Scaffold for Polyadenosine-Diphosphate-Ribose Polymerase 14 (PARP14) Macrodomain 2.” Bioorganic and Medicinal Chemistry 26 (11): 2965–72.
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Files:: Moustakim-et-al-2018-Bioorganic-and-Medicinal-Chemistry.pdf

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Publisher copy:: 10.1016/j.bmc.2018.03.020

Authors

+ Moustakim, M More by this author

Institution:: University of Oxford
Division:: MPLS Division
Department:: Chemistry
Role:: Author

+ Riedel, K More by this author

Role:: Author

+ Schuller, M More by this author

Institution:: University of Oxford
Division:: Medical Sciences Division
Department:: NDM; Structural Genomics Consortium
Role:: Author

+ Gehring, A More by this author

Role:: Author

+ Monteiro, O More by this author

Institution:: University of Oxford
Division:: Medical Sciences Division
Department:: NDM; Structural Genomics Consortium
Role:: Author

More authors...

+ Engineering and Physical Sciences Research Council More from this funder

Grant:: EP/L015838/1

+ Structural Genomics Consortium More from this funder

Publisher:: Elsevier
Journal:: Bioorganic and Medicinal Chemistry More from this journal
Volume:: 26
Issue:: 11
Pages:: 2965-2972
Publication date:: 2018-03-12
Acceptance date:: 2018-03-10
DOI:: 10.1016/j.bmc.2018.03.020
EISSN:: 1464-3391
ISSN:: 0968-0896

Keywords:: macrodomain

inhibitor design

Poly-ADP ribsose

PARP
Pubs id:: pubs:829044
UUID:: uuid:edf58132-1261-4d58-8102-7783253d1470
Local pid:: pubs:829044
Deposit date:: 2018-03-12

Terms of use

Copyright holder:: Moustakim et al
Copyright date:: 2018
Notes:: Copyright © 2018 The Authors. Published by Elsevier Ltd. Open Access funded by Wellcome Trust, available under a Creative Commons license.

Licence:: CC Attribution (CC BY)

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