PXD007523
PXD007523 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Kinome-wide chemoproteomics characterization of pyrrolo[3,4-c]pyrazols as potent and selective inhibitors of glycogen synthase kinase 3 |
| Description | Glycogen synthase kinase 3 has evolutionarily conserved roles in cell signaling and metabolism and is a recognized drug target in neurological pathologies, most prominently bipolar disorder. More recently it has been suggested that GSK3 may be a target for the treatment of trypanosomatid parasite infections, e.g. with T. brucei, due to the lethal phenotype observed in parasite GSK3 short RNAi knockdown experiments. Here we investigated the kinome selectivity of a library of pyrrolo[3,4-c]pyrazol inhibitors that were developed against T. brucei GSK3 but that also interact with the human orthologue and other protein kinases. We applied label-free MS-based kinome chemoproteomics profiling with kinobeads to obtain the selectivity profiles of all 39 library members against 217 human protein and lipid kinases. This allowed us to study the structure-activity relationship of the library members as well as the chemical genetic relationships between kinase targets. As a result, we identified a novel and highly selective HsGSK3 inhibitor containing a 2-chloroaniline-substituted squaric acid amide pharmacophore that confers low nanomolar (IC50 = 2.8 nM) and sub-micromolar potency against purified and cellular HsGSK3. The inhibitor will be useful as a new lead for GSK3 inhibitor development and as a chemical genetic probe to study roles of GSK3 in cell signaling. |
| HostingRepository | MassIVE |
| AnnounceDate | 2019-01-02 |
| AnnouncementXML | Submission_2019-01-02_13:24:18.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Martin Golkowski |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | unknown modification: PRIDE:0000398 |
| Instrument | LTQ Orbitrap Elite |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2017-08-21 14:40:59 | ID requested | |
| ⏵ 1 | 2019-01-02 13:24:18 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: T.Brucei, GSK3, Kinase Inhibitor, Chemoproteomics |
Contact List
| Shao-En Ong | |
|---|---|
| contact affiliation | University of Washington |
| contact email | shaoen@uw.edu |
| lab head | |
| Martin Golkowski | |
| contact affiliation | University of Washington |
| contact email | golkom@uw.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000081471 |
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