- Abstract:
- Bromodomain containing proteins PB1, SMARCA4, and SMARCA2 are important components of SWI/SNF chromatin remodeling complexes. We identified bromodomain inhibitors that target these proteins and display unusual binding modes involving water displacement from the KAc binding site. The best compound binds the fifth bromodomain of PB1 with a KD of 124 nM, SMARCA2B and SMARCA4 with KD values of 262 and 417 nM, respectively, and displays excellent selectivity over bromodomains other than PB1, SMARCA2, and SMARCA4.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
- Version:
- Publisher's version
- Files:
-
-
(pdf, 3.4MB)
-
- Publisher copy:
- 10.1021/acs.jmedchem.5b01997
-
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- Funding agency for:
- Sutherell, CL
- Funding agency for:
- Ley, SV
- Publisher:
- American Chemical Society Publisher's website
- Journal:
- Journal of medicinal chemistry Journal website
- Volume:
- 59
- Issue:
- 10
- Pages:
- 5095-5101
- Publication date:
- 2016-04-27
- DOI:
- EISSN:
-
1520-4804
- ISSN:
-
0022-2623
- Pubs id:
-
pubs:619949
- URN:
-
uri:6a445819-669d-404b-aee8-804e03dfdff1
- UUID:
-
uuid:6a445819-669d-404b-aee8-804e03dfdff1
- Local pid:
- pubs:619949
- Paper number:
- 10
- Copyright holder:
- © 2016 American Chemical Society
- Copyright date:
- 2016
- Notes:
- This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Journal article
Identification and development of 2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one inhibitors targeting bromodomains within the switch/sucrose nonfermenting complex
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+ Cambridge Ph.D. Training Programme in Chemical Biology and Molecular Medicine
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+ Engineering and Physical Sciences Research Council
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