Ask about this productRelated genes to: SHP2 antibody
- Gene:
- PTPN11 NIH gene
- Name:
- protein tyrosine phosphatase non-receptor type 11
- Previous symbol:
- NS1
- Synonyms:
- BPTP3, SH-PTP2, SHP-2, PTP2C, SHP2
- Chromosome:
- 12q24.13
- Locus Type:
- gene with protein product
- Date approved:
- 1993-03-03
- Date modifiied:
- 2019-04-23
Related products to: SHP2 antibody
Related articles to: SHP2 antibody
- is retracting the article titled "Protein Tyrosine Phosphatase Non-Receptor 11 (/Shp2) as a Driver Oncogene and a Novel Therapeutic Target in Non-Small Cell Lung Cancer (NSCLC)" [...]. - Source: PubMed
Publication date: 2026/04/29
Richards Cathy EElamin Yasir YCarr AoifeGately KathyRafee ShereenCremona MattiaHanrahan EmerSmyth RobertRyan DanielMorgan Ross KKennedy SusanHudson LanceFay JoannaO'Byrne KennethHennessy Bryan TToomey Sinead - Targeted covalent inhibitors (TCIs) form covalent bonds with a specific amino acid in their target proteins, offering high selectivity and sustained pharmacologic effects. However, identifying optimal electrophilic warheads and nucleophilic amino acids remains a major hurdle for TCI development. While covalent fragment libraries are efficient in the identification of reactive residues, their inherently weak and transient interactions often fail to address functionally relevant binding sites. Here, we combine the exploratory approach of covalent fragment screening with established inhibitor pharmacophores for covalent mapping of the tunnel allosteric site of the oncogenic phosphatase SHP2. Aryl sulfonyl fluoride (SF) fragments featuring pharmacophore elements to enhance noncovalent interactions (target-biased fragments) covalently targeted lysine 492 (K492) in the tunnel binding site, while a conventional SF fragment library lacking these features was not reactive toward K492. Covalent engagement of K492 improved enzyme inhibition and provides a starting point for SHP2 TCI development. More broadly, this study underscores how noncovalent interactions direct covalent fragment binding and highlights target-biased fragments as a complementary strategy to conventional covalent fragment libraries to identify suitable warheads and reactive amino acids in functionally relevant binding sites with minimal a priori knowledge of ligand pharmacophores. - Source: PubMed
Efrém Nina-LouisaCsorba NoémiAmoussa MachoudÁbrányi-Balogh PéterGuo ZiqiongPetri LászlóBo FengDi Lorenzo VincenzoRoske YvetteSzalai Tibor ViktorMihalovits LeventeSimon JózsefLi JiaDaumke OliverKeserű György MNazaré Marc - Genetic testing in neurofibromatosis type 1 (NF1) occasionally reveals two heterozygous variants in the same individual. Correct interpretation hinges on allelic phasing, elucidation of somatic second hits in lesions, and distinction from bona fide dual RASopathy diagnoses. We provide a focused, critical review of the primary literature on (i) doublets in , (ii) purported germline configurations—particularly in spinal neurofibromatosis, (iii) biallelic somatic inactivation of in café-au-lait macules, tumors, and juvenile myelomonocytic leukemia, and (iv) confirmed cases of dual RASopathy. We also include an index patient with two heterozygous variants to illustrate clinical challenges. Phase-proven doublets are rare, often closely spaced, and generally accompany classic NF1 without reproducible phenotype escalation. Claims of germline pathogenic variants weaken on reappraisal: second alleles reported in spinal neurofibromatosis typically do not meet current pathogenicity standards, while Nf1−/− mouse embryonic lethality underscores the biological implausibility of constitutive biallelic loss. In contrast, biallelic somatic inactivation is pervasive across NF1 lesions, including café-au-lait macules, plexiform and cutaneous neurofibromas, and juvenile myelomonocytic leukemia, due to mitotic recombination (copy-neutral loss-of-heterozygosity), microdeletions, or a second variant. Confirmed dual RASopathy diagnoses (most often plus ) are rare and produce blended systemic phenotypes. Interpretation of double findings should prioritize independent American College of Medical Genetics and Genomics/Association for Molecular Pathology classification of each variant, rigorous phasing (segregation/RNA/allele-specific methods), and tumor-focused analysis where applicable. Our index case and synthesis support a practical workflow that clarifies counseling and helps avoid over-calling dual pathogenicity. - Source: PubMed
Publication date: 2026/04/15
Angelova-Toshkina DanielaSchanze DennyVaassen PiaFrühwald Michael CRosenbaum ThorstenZenker MartinKuhlen Michaela - Type 2 diabetes mellitus (T2DM), a chronic metabolic disorder caused by genetic and environmental factors, is characterized by insulin resistance and impaired pancreatic β-cell function. Hyperoside, a natural flavonol glycoside, exerts anti-T2DM effects, but its mechanism remains unclear. This study established T2DM mouse models via a high-fat/high-sugar diet and streptozotocin injection, detecting body weight, blood glucose, and biochemical indicators. Combined metabolomics, network pharmacology, in-vitro experiments, and molecular docking were used to explore its therapeutic targets and mechanisms. Pharmacodynamic studies confirmed hyperoside's hypoglycemic and symptom-improving effects. Nontargeted metabolomics identified 15 diabetes-related biomarkers, revealing hyperoside may regulate primary bile acid biosynthesis and glycerophospholipid metabolism via specific targets. Network pharmacology screened 161 core targets, with SRC, PTPN11, and EGFR as key ones via KEGG enrichment analysis. Molecular docking verified hyperoside's favorable binding affinity to these targets. In conclusion, hyperoside has a good therapeutic effect on T2DM, possibly by regulating the above metabolic pathways. - Source: PubMed
Zhao YueqiYang YueLi YingLi XiaoyuHou SiyuWan ChunleiWang ShimingSa QilaZhang Lei - Hippocampal sclerosis is a frequent finding in pediatric epilepsy surgery and has traditionally been regarded as an acquired lesion. It commonly co-occurs with focal cortical dysplasia (FCD IIIa), yet whether hippocampal injury is secondary to seizures or reflects a shared underlying etiology remains unresolved. Here we identified somatic variants activating the RAS-MAPK pathway in 40% of patients with hippocampal sclerosis, but in none with non-sclerotic hippocampus. Gain-of-function variants in were the most common finding, with mutations present in both cortex and hippocampus and enriched in hippocampal neurons, consistent with a shared developmental origin. In mice, mutants developed profound hippocampal degeneration and gliosis following subthreshold kainic acid exposure, whereas wild-type controls were unaffected. p38-dependent stress pathways were upregulated in patients and mice, suggesting a mechanism through which ERK-p38 crosstalk lowers the threshold for seizure-induced injury. These results provide a genetic explanation for FCD IIIa, elucidate the role of somatic mutations within the RAS-MAPK pathway in driving hippocampal sclerosis, and provide a target for pathway-specific interventions for intractable seizures. - Source: PubMed
Publication date: 2026/04/09
Mashburn-Warren LaurenHolub AshtonSran SahibjotRamadesikan SwethaSuh Keaton RThompson AllisonAnderson James JRivaldi AditheZavarella Ari RChandler MeganDaley AllisonStrawser Corinne HGarfinkle Elizabeth A RPindrik JonathanShaikhouni AmmarLeonard JeffreyBoué Daniel RThomas Diana LPierson Christopher RMardis Elaine RMiller Katherine EOstendorf Adam PKoboldt Daniel CBedrosian Tracy A