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
- Germline genetic susceptibility to pediatric acute lymphoblastic leukemia (pALL) remains incompletely characterized across the allelic spectrum, including ultra-rare, high-penetrance cancer predisposing variants (CPVs). - Source: PubMed
Publication date: 2026/05/06
Meng XiaoxiChen ChengQin NaMulder Heather LEaston JohnEdmonson Michael NRusch MichaelZhang JinghuiMyers Jason RSpector Logan GTurcotte Lucie MChanock Stephen JYang Jun JNichols Kim EPui Ching-HonXu JianMullighan Charles GHudson Melissa MNess Kirsten KArmstrong Gregory TChatterjee NilanjanIm CindyWang Zhaoming - : Hepatitis B virus (HBV) infection continues to be a major public health concern, especially in sub-Saharan Africa, where widespread epidemics and restricted availability of long-term antiviral therapies result in higher mortality and morbidity rates. Drug repurposing represents a strategic approach to accelerate the discovery of effective therapies by leveraging agents with demonstrated antiviral and immunomodulatory activity. Product Nkabinde (PN) is a patented African polyherbal formulation initially developed for the treatment of HIV. Recent experimental studies demonstrate PN's potent anti-HIV activity and significant immunomodulatory effects in human immune cells, implicating host-directed mechanisms relevant to chronic viral infections. This study combines an integrative application of network pharmacology and molecular docking to evaluate the repurposing potential of PN as a multi-target agent in HBV. : Bioactive components of PN were screened, and compound-associated targets were intersected with HBV-associated genes (proteins) to construct a protein-protein interaction (PPI) network. Topological analysis identified 10 hub targets (STAT1, STAT3, SRC, HCK, EGFR, SYK, PIK3CA, PIK3CB, PIK3R1, and PTPN11). Gene Ontology and KEGG pathway enrichment were performed with an FDR cut-off < 0.05. Significantly enriched pathways included JAK-STAT signaling, chemokine signaling, EGFR-TKI resistance, PI3K complex signaling, and viral infection pathways, particularly those related to Kaposi sarcoma virus and HSV-1, indicating immunoregulatory and antiviral roles. Molecular docking was performed using AutoDock Vina 1.1.2 to evaluate binding affinity and interaction mode of key PN phytochemicals against the hub proteins, and results were compared to their respective co-crystallized ligands. : Molecular docking indicated that major phytochemicals from PN exhibited significant binding affinities across all 10 hub host targets, typically outperforming or closely matching their respective co-crystallized ligands. The strongest contacts were observed for β-sitosterol-PIK3CB (-14.2 kcal/mol) and oleanolic acid-SYK (-14.0 kcal/mol), which were significantly stronger than the co-crystallized ligands (-7.9 and -8.3 kcal/mol, respectively), indicating robust stabilization within catalytic and regulatory pockets. Procyanidin B2 toward HCK (-10.5 vs. -7.9 kcal/mol) and PIK3CA (-9.5 vs. -7.3 kcal/mol), quercetin toward PIK3R1 (-10.6 vs. -8.2 kcal/mol) and PTPN11 (-9.2 vs. -7.5 kcal/mol), rutin toward SRC (-10.5 vs. 7.8 kcal/mol), and diosgenin toward EGFR (-9.4 vs. 8.4 kcal/mol). Procyanidin B2 maintained robust multi-hydrogen bonding networks, demonstrating significant binding, despite STAT1 and STAT3 docking showing identical affinities to co-crystals. Conserved hydrogen bonds, π-cation interactions, and significant hydrophobic packing at ATP-binding clefts and regulatory domains supported these interaction patterns, indicating competitive suppression of host signaling nodes taken over by HBV. : Together, these results demonstrate that the components of PN possess strong multitarget binding capabilities across the PI3K/AKT, JAK-STAT, SRC-family kinase, EGFR, and SYK pathways, supporting their potential repurposing as host-directed HBV therapeutics with the ability to impede immune evasion, viral persistence, and HBV-associated oncogenic progression. - Source: PubMed
Publication date: 2026/04/16
Ugbaja Samuel ChimaNkabinde Siphathimandla AuthorityNkabinde MaguguGqaleni Nceba - : RASopathies represent a clinically and genetically diverse group of syndromes resulting from germline mutations in genes regulating the RAS/mitogen-activated protein kinase (MAPK) signaling cascade. : The aim of this study was to describe the clinical features and genetic variants identified in patients with genetically confirmed Noonan syndrome (NS) in a limited cohort from Romania. A total of 25 patients with positive genetic testing for NS-associated genes were included. Genetic testing was performed primarily using next-generation sequencing. : A total of twenty-six variants were identified in twenty-five patients, as one patient carried two pathogenic variants in the gene (c.188A>G and c.922A>G). Of these variants, twenty-four (92.31%) were classified as pathogenic and two (7.69%) as variants of uncertain significance (VUS). Pathogenic variants were found in different genes, including , , , and , with being the most frequently affected gene. Males predominated (17/25), with a male-to-female ratio of approximately 2:1. Two patients inherited the pathogenic variant from an affected parent. Cardiovascular involvement was present in 21 patients (84%), with pulmonary valve stenosis (PVS) being the most common finding (48%), followed by hypertrophic cardiomyopathy (16%). Additional cardiac anomalies included atrial septal defect, valvular regurgitation, dysplastic valves, coarctation of the aorta, and sinotubular junction narrowing. Short stature was observed in 64% of patients, and craniofacial dysmorphism was present in 96%. Cutaneous, ectodermal, dental, ophthalmologic, and auditory manifestations were variably observed. : Although based on a limited cohort from Romania, this study provides insights into clinical features suggestive of NS. Our findings highlight the genetic heterogeneity of NS and emphasize the importance of comprehensive genetic testing for confirming diagnosis, guiding clinical management, and supporting family counseling. - Source: PubMed
Publication date: 2026/04/17
Nazarie Florina VictoriaDobrescu Mihaela AmeliaLazea CeciliaDavid Ana AdrianaȘufană CrinaBucerzan SimonaCainap Simona SoranaRancea RalucaStănoiu-Pînzariu OanaPascanu Ionela MariaPopp Radu AnghelPop Laura AncutaLazăr CălinAlkhzouz CameliaMiclea DianaVulturar Romana - 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