{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cho HJ"],"funding":["UK Research and Innovation (UKRI)","British Heart Foundation","Cancer Research UK","Barts Charity","Medical Research Council","NIHR | National Institute for Health and Care Research Applied Research Collaboration Oxford and Thames Valley","UK Research and Innovation","UKRI | Medical Research Council"],"pagination":["2115-2136"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12340136"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(8)"],"pubmed_abstract":["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. SFX-01, an α-cyclodextrin-stabilized sulforaphane complex currently in clinical development, covalently adducts cysteine residues. Using unbiased proteomics, its protein targets were identified, including 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 normalized their phosphatase activity and myeloid cell count. Furthermore, SFX-01 also attenuated JMML human patient-derived hematopoie"],"journal":["EMBO molecular medicine"],"pubmed_title":["SFX-01 is therapeutic against myeloproliferative disorders caused by activating mutations in Shp2."],"pmcid":["PMC12340136"],"funding_grant_id":["EP/Y027698/1","MR/R01065X/2","C16420/A18066","MGU0401","Cardiovascular Programme Award G00913"],"pubmed_authors":["Schroder E","Yin X","Lynham S","Prysyazhna O","Fernandez-Caggiano M","Cutillas PR","Louka E","Switzer CH","Eaton P","Smith J","Mayr M","Bianchi K","Yang X","Mead AJ","Rajeeve V","de Jesus DS","Cho HJ","Morales V","Charles RL","Eminaga S"],"additional_accession":[]},"is_claimable":false,"name":"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. SFX-01, an α-cyclodextrin-stabilized sulforaphane complex currently in clinical development, covalently adducts cysteine residues. Using unbiased proteomics, its protein targets were identified, including 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 normalized their phosphatase activity and myeloid cell count. Furthermore, SFX-01 also attenuated JMML human patient-derived hematopoie","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-29T17:55:43.117Z","creation":"2026-05-18T03:07:20.623Z"},"accession":"S-EPMC12340136","cross_references":{"pubmed":["40640547"],"doi":["10.1038/s44321-025-00267-7"]}}