PXD047599
PXD047599 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | A high affinity pan-PI3K binding module supports selective targeted protein degradation of PI3Ka |
| Description | Class I phosphoinositide 3-kinases (PI3Ks) control cellular growth, but are also essential in insulin signaling and glucose homeostasis. Pan-PI3K inhibitors thus generate substantial adverse effects, a reality that has plagued drug development against this target class. We present here evidence that a high affinity binding module with the capacity to target all class I PI3K isoforms can facilitate selective degradation of the most frequently mutated class I isoform, PI3Ka, when incorporated into a cereblon-targeted (CRBN) degrader. A systematic proteomics study guided the fine tuning of molecular features to optimize degrader selectivity and potency. Our work resulted in the creation of WJ112-14, a PI3Ka-specific nanomolar degrader that should serve as an important research tool for studying PI3K biology. Given the toxicities observed in the clinic with unselective PI3Ka inhibitors, the results here offer a new approach toward selectively targeting this frequently mutated oncogenic driver. |
| HostingRepository | MassIVE |
| AnnounceDate | 2023-12-12 |
| AnnouncementXML | Submission_2023-12-12_05:20:56.173.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | danilo ritz |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | TMTpro |
| Instrument | Orbitrap Fusion Lumos; Orbitrap Eclipse |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2023-12-06 23:21:19 | ID requested | |
| ⏵ 1 | 2023-12-12 05:20:56 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: PI3Ka, degrader |
Contact List
| Alexander Schmidt | |
|---|---|
| contact affiliation | Biozentrum, Universtiy of Basel, 4056 Basel, Switzerland |
| contact email | alex.schmidt@unibas.ch |
| lab head | |
| danilo ritz | |
| contact affiliation | University of Basel |
| contact email | danilo.ritz@unibas.ch |
| 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/MSV000093594/ |
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