Journal article
Covalent targeting of remote cysteine residues to develop CDK12 and 13 inhibitors
- Abstract:
-
Cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) play critical roles in the regulation of gene transcription. However, the absence of CDK12 and CDK13 inhibitors has hindered the ability to investigate the consequences of their inhibition in healthy cells and cancer cells. Here we describe the rational design of a first-in-class CDK12 and CDK13 covalent inhibitor, THZ531. Co-crystallization of THZ531 with CDK12–cyclin K indicates that THZ531 irreversibly targets a cysteine located outside ...
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- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
-
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(Accepted manuscript, pdf, 29.2MB)
-
(Accepted manuscript, pdf, 32.0MB)
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(Accepted manuscript, pdf, 245.5KB)
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- Publisher copy:
- 10.1038/nchembio.2166
Authors
Funding
+ National Institutes of Health
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Funding agency for:
Young, R
Gray, N
Grant:
CA109901
5 R01 CA179483-02 C
+ Deutsche Forschungsgemeinschaft
More from this funder
Funding agency for:
Geyer, M
Grant:
GE 976/9-1
+ Koch Institute and Dana–Farber/Harvard Cancer Center Bridge Grant
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Funding agency for:
Kwiatkowski, N
Young, R
Gray, N
Grant:
CA109901
5 R01 CA179483-02 C
+ Hope Funds for Cancer Research Grillo-Marxuach Family Fellowship
More from this funder
Funding agency for:
Abraham, B
Bibliographic Details
- Publisher:
- Nature Publishing Group Publisher's website
- Journal:
- Nature Chemical Biology Journal website
- Volume:
- 12
- Pages:
- 876-884
- Publication date:
- 2016-08-29
- Acceptance date:
- 2016-05-13
- DOI:
- EISSN:
-
1552-4469
- ISSN:
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1552-4450
Item Description
- Keywords:
- Pubs id:
-
pubs:627889
- UUID:
-
uuid:9d39c81e-0d3a-407a-9fb0-c128870235ab
- Local pid:
- pubs:627889
- Source identifiers:
-
627889
- Deposit date:
- 2016-06-14
Terms of use
- Copyright holder:
- Zhang et al
- Copyright date:
- 2016
- Notes:
- This is the accepted manuscript version of the article. The final version is available online from Nature at: https://doi.org/10.1038/nchembio.2166
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