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PXD035999

PXD035999 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDual inhibition of SHP2 and autophagy suppresses NF1-associated malignant peripheral nerve sheath tumors
DescriptionMalignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of premature death for patients with Neurofibromatosis type 1 and no approved targeted therapies are available. Benign plexiform neurofibromas have been successfully treated with selumetinib, a MEK inhibitor, but after progression to MPNST, MEK inhibition alone is not effective. Frequently, adaptive responses to single agent targeted inhibitors invokes alterations in receptor tyrosine kinase expression and feedback regulation that leads to inhibitor bypass. Here, the effects of SHP099, an inhibitor of the protein-tyrosine phosphatase SHP2 (encoded by the PTPN11 gene) was tested alone and in combination with trametinib (MEKi) in an orthotopic implantation murine model of NF1 MPNST with defined genotype (NP, Nf1-/-;Trp53-/-). Kinase enrichment proteomic analysis was performed using tumor tissue from vehicle, SHP099, trametinib, or trametinib and SHP099 in combination for 5 or 21 days to evaluate the effects on the functional kinome.
HostingRepositoryPRIDE
AnnounceDate2024-11-20
AnnouncementXMLSubmission_2024-11-20_08:51:49.140.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSteven Angus
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-08-12 03:17:28ID requested
12024-11-20 08:51:49announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: SHP099, therapeutics, patient-derived xenograft, kinase inhibitor, genetically engineered mouse model, hydroxychloroquine,Neurofibromatosis type 1, trametinib, kinome
Contact List
Luis F. Parada
contact affiliationMemorial Sloan Kettering Cancer Center
contact emailparadal@mskcc.org
lab head
Steven Angus
contact affiliationIndiana University School of Medicine
contact emailsangus@iu.edu
dataset submitter
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Dataset FTP location
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