Proteomics

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SFX-01 is therapeutic against myeloproliferative disorders caused by activating mutations in Shp2

ABSTRACT: • Activating mutations of Shp2 cause conditions such as Noonan syndrome and juvenile myelomonocytic leukemia (JMML), with unmet therapeutic needs. • SFX-01, a sulforaphane complex, modifies cysteine residues and targets proteins including Shp2, where it induces an inhibitory modification at the active site of this protein phosphatase. • In a transgenic mouse model of Noonan syndrome and human JMML stem cells, SFX-01 normalized Shp2 activity, reduced myeloid cell counts, and induced cell-cycle arrest, highlighting its therapeutic potential.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Myeloid Cell, Bone Marrow

DISEASE(S): Juvenile Myelomonocytic Leukemia

SUBMITTER: Vinothini Rajeeve  

LAB HEAD: Professor Pedro Cutillas

PROVIDER: PXD061655 | Pride | 2025-06-12

REPOSITORIES: Pride

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QE1_MS_567_Hyunju_PP_Sample_1HET.mgf Mgf
QE1_MS_567_Hyunju_PP_Sample_1HET.mzid Mzid
QE1_MS_567_Hyunju_PP_Sample_1HET.raw Raw
QE1_MS_567_Hyunju_PP_Sample_1HETD.mgf Mgf
QE1_MS_567_Hyunju_PP_Sample_1HETD.mzid Mzid
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Publications

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 dithiolethio  ...[more]

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