Dataset
LIM domain kinase 1 (LIMK1), human kinase domain; A Target Enabling Package
- Documentation:
- A description of the materials and methods is included within the TEP datasheet. Loss of the translational repressor FMRP in fragile X syndrome causes upregulation of the type II BMP receptor BMPR2 and its non-canonical signalling via the kinase LIMK1. LIMK1 performs inhibitory phosphorylation on cofilin proteins blocking their actin-severing activity. Excessive BMPR2-LIMK1 activation was associated with dendritic spine and behavioural defects in animal models that could be rescued by BMPR2 knockdown or LIMK1 inhibition. Here we present a target enabling package for the therapeutic target LIMK1. We include crystal structures of BMPR2, LIMK1, LIMK2 and the LIMK1-cofilin complex, as well as multiple assays for small molecule inhibitor screening. Finally, we identify a series of allosteric LIMK1 inhibitors with promising potency and selectivity that may potentially allow the development of a safe drug for this chronic indication.
- Version:
- 1
Actions
Access Document
- Files:
-
-
(Preview, pdf, 1.2MB, Terms of use)
-
Authors/Creators
Contributors
+ Salah, E
- Institution:
- University of Oxford
- Division:
- MPLS
- Department:
- Chemistry
- Sub department:
- Organic Chemistry
- Role:
- Researcher
+ Knapp, S
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- NDM
- Sub department:
- Target Discovery Institute
- Role:
- Researcher
+ Beltrami, A
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- NDM
- Sub department:
- Structural Genomics Consortium
- Role:
- Researcher
+ Chaikuad, A
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- NDM
- Sub department:
- Structural Genomics Consortium
- Role:
- Researcher
+ Hanke, T
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- NDM
- Sub department:
- Target Discovery Institute
- Role:
- Researcher
- Publisher:
- University of Oxford
- Publication date:
- 2018
- Version number:
- 1
- DOI:
- Keywords:
- Subjects:
- Pubs id:
-
1480000
- UUID:
-
uuid:1b3f34b2-5c3e-40ba-8b76-f6e687fd71d4
- Local pid:
-
pubs:1480000
- Deposit date:
-
2018-04-04
- ARK identifier:
Terms of use
- Copyright date:
- 2018
If you are the owner of this record, you can report an update to it here: Report update to this record