PXD061882

PXD061882 is an original dataset announced via ProteomeXchange.

Title	SFX-01 is therapeutic against myeloproliferative disorders caused by activating mutations in Shp2
Description	Activating mutations of Src homology-2 domain-containing protein tyrosine phosphatase-2 (Shp2) cause multiple childhood conditions for which there is an unmet therapeutic need, including juvenile myelomonocytic leukemia (JMML) and Noonan syndrome. Using unbiased proteomics, the protein targets of SFX-01, an α-cyclodextrin-stabilized isothiocyanate complex that covalently adducts cysteines that is in clinical development, were identified and included Shp2. SFX-01 induced an inhibitory dithiolethione modification at the Shp2 active site cysteine. Importantly, in a transgenic mouse model of human Noonan syndrome with hyperactive D61G Shp2, SFX-01 concomitantly normalised their phosphatase activity and myeloid cell count. Furthermore, SFX-01 also attenuated JMML human patient-derived hematopoietic stem cell proliferation that was linked to STAT1 signaling and decreased cyclin D1 expression, resulting in cell-cycle arrest. We conclude that SFX-01 is an activating mutant Shp2 inhibitor and may offer beneficial effects in patients with JMML or Noonan syndrome.
HostingRepository	PRIDE
AnnounceDate	2025-06-13
AnnouncementXML	Submission_2025-06-13_09:47:29.328.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD061882
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	XIAOKE YIN
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-15 14:45:43	ID requested
⏵ 1	2025-06-13 09:47:29	announced

10.6019/PXD061882;

submitter keyword: Sulforaphane,Homology 2 Containing Protein Tyrosine Phosphatase 2, juvenile myelomonocytic leukemia

Manuel Mayr
contact affiliation	National Heart & Lung Institute, Imperial College London, London, UK
contact email	m.mayr@imperial.ac.uk
lab head
XIAOKE YIN
contact affiliation	National Heart and Lung Institute, Faculty of Medicine, Imperial College London
contact email	xiaoke.yin@imperial.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD061882
     1. Label: PRIDE project
     2. Name: SFX-01 is therapeutic against myeloproliferative disorders caused by activating mutations in Shp2