Ask about this productRelated genes to: USP7 antibody
- Gene:
- USP7 NIH gene
- Name:
- ubiquitin specific peptidase 7
- Previous symbol:
- HAUSP
- Synonyms:
- -
- Chromosome:
- 16p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1998-10-12
- Date modifiied:
- 2017-01-04
Related products to: USP7 antibody
Related articles to: USP7 antibody
- : Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that regulates multiple oncogenic and tumor-suppressive pathways and has emerged as a promising target for anticancer drug discovery. However, most reported USP7 inhibitors belong to a limited number of structural classes, and no USP7-targeted therapy has yet reached clinical application. This study aimed to identify structurally diverse candidate USP7-inhibitory scaffolds with antiproliferative activity using an integrated computational and experimental screening strategy. : A drug discovery workflow combining pharmacophore modelling, structure-based virtual screening, molecular docking, and in silico pharmacokinetic assessment was employed to identify candidate USP7 inhibitors. Selected compounds were evaluated for inhibition of recombinant USP7 and for antiproliferative activity in a panel of human cancer cell lines. Molecular docking analyses were performed to investigate predicted binding modes. : The primary screening campaign identified four active compounds (>50% inhibition at 10 µM) and twenty-one weakly active compounds (10-49% inhibition at 10 µM), including structurally distinct approved drugs and compounds from an in-house chemical library. The four active compounds were subsequently validated by dose-response assays against recombinant USP7 and exhibited micromolar inhibitory activity. These candidate USP7-inhibitory scaffolds also exhibited antiproliferative activity across cancer cell lines with different molecular backgrounds. Docking studies predicted binding within a pharmacologically relevant region of the USP7 catalytic cleft and revealed putative interactions with key residues involved in ligand recognition. Among the compounds evaluated, rafoxanide demonstrated the most favorable combination of predicted USP7 binding and antiproliferative activity. : This integrated virtual screening and experimental validation approach enabled the identification of candidate USP7-inhibitory scaffolds with preliminary antiproliferative activity. The identified hits include approved drugs with previously unreported USP7 inhibitory activity, as well as underexplored scaffolds that expand the chemical space of candidate USP7-targeting molecules. These candidate scaffolds warrant further medicinal chemistry optimization, orthogonal validation, and mechanistic characterization to establish their potential as USP7-targeted anticancer agents. - Source: PubMed
Publication date: 2026/08/03
Oliveira Rita IFranco CaioMano MiguelLeal Ana SSalvador Jorge A R - Hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ /HER2-) breast cancer is the most common subtype in females, frequently challenged by resistance to endocrine therapy and CDK4/6 inhibitors. Here we show that N-acetylneuraminate synthase (NANS) is significantly upregulated in female HR+ /HER2- breast cancer patients, inversely correlating with patient prognosis. Functionally, NANS promotes tumor growth and confers resistance to tamoxifen and CDK4/6 inhibitors independently of its canonical enzymatic activity. Mechanistically, NANS recruits ubiquitin-specific protease 7 (USP7) to deubiquitinate and stabilize large tumor suppressor kinase 2 (LATS2), leading to canonical Hippo pathway activation and upregulation of estrogen receptor α and CDK4. Reintroducing LATS2 into NANS-depleted cells partially rescues the impaired growth-promoting and drug-resistant phenotypes in vitro and in vivo. Furthermore, the clinical relevance of the NANS-USP7/LATS2 axis is confirmed in patient-derived female HR+ /HER2- breast cancer samples. Together, our findings unveil an enzymatic activity-independent role for NANS in driving therapy resistance, nominating it as a promising therapeutic target. - Source: PubMed
Publication date: 2026/07/24
Cai Jia-YangHuang Min-YingYang Shao-YingZhang Fang-LinZhang Yin-LingAndriani LisaZhao QianCao A-YongLi Da-QiangShao Zhi-Ming - Inflammatory diseases impose a significant global healthcare burden, necessitating the development of effective anti-inflammatory agents. Many clinically used drugs are isolated from plants or derived from natural products via semi-synthetic procedures. Among natural products, coumarins have demonstrated broad-spectrum pharmacological activities. This study investigates the anti-inflammatory mechanisms of an uncommon natural coumarin, 7-methoxy-8-isopentenyloxycoumarin (7MI), isolated from the seed of the higher Mediterranean plant Magydaris pastinacea. 7MI's effects were assessed in LPS-stimulated Raw264.7 macrophages using immunoblotting, RT-qPCR, ChIP assay, chase assay, reporter assay, ELISA, phosphatase activity assay, and transfection. 7MI significantly reduced the release of pro-inflammatory cytokines, including IL-6 and MCP-1, and suppressed cyclooxygenase-2 (COX-2) expression. Mechanistically, 7MI attenuated canonical LPS-induced TLR4 signaling by inhibiting the parallel activation of the NF-κB and MAPK/AP-1 pathways. 7MI blocked NF-κB p65 nuclear translocation and its transcriptional activity. Concurrently, 7MI enhanced MAPK phosphatase-1 (MKP-1) activity, which deactivated p38MAPK, thereby dampening activation of AP-1 and the synergistic transcription factor CCAAT/enhancer-binding protein (C/EBP)β. Beyond transcriptional suppression, 7MI exerted a distinct post-translational effect by accelerating COX-2 proteasomal degradation through inhibition of the deubiquitinases USP7 and USP22, leading to enhanced K48-linked polyubiquitination of the COX-2 protein. Crucially, in vivo administration of 7MI dramatically improved survival rate and mitigated multi-organ damage in a murine model of fatal sepsis. These findings suggest that 7MI exerts broad-spectrum anti-inflammatory effects by simultaneously suppressing canonical TLR4-driven transcriptional cascades to halt de novo inflammatory mediator synthesis and by promoting pro-inflammatory protein clearance, highlighting its potential as a lead compound for LPS-associated inflammatory disorders. - Source: PubMed
Publication date: 2026/08/21
Huang Shiu-WenChen Hsiu-ChenLupia AntonioMeleddu RitaDistinto SimonaMaccioni EliasChuang Chin-HuiCottiglia FilippoHsu Ming-Jen - Myeloproliferative neoplasms (MPN) are shaped by epigenetic rewiring that extends beyond canonical JAK2V617F-driven signaling. This review argues that context-dependent chromatin states, not merely genetic lesions, determine disease trajectory, fibrotic transformation, and leukemic progression. We synthesize recent evidence indicating that PRC2 deficiency is supported by the strongest MPN-specific evidence for BRD4 dependency, whereas PARP/BCL-2 vulnerabilities associated with TET2/IDH mutations and USP7 dependency associated with ASXL1 remain supported primarily by related myeloid malignancies or preclinical studies. Introducing the concept of an "epigenetic clock" of clonal evolution, we propose that MPN cells acquire progressively pathological chromatin states that can be quantified through composite methylation and accessibility scores. Importantly, temporal synthetic lethality, using short epigenetic pulses to remodel chromatin before applying targeted agents, offers a rational scheduling strategy to expose non-redundant dependencies while sparing normal hematopoiesis. We outline a translational roadmap incorporating cfDNA methylome biomarkers, ongoing BET inhibitor trials, and emerging single-cell perturbation approaches. Finally, we highlight the "dark epigenome" of repetitive elements as an unexplored therapeutic frontier. Collectively, these findings suggest that context-restricted chromatin vulnerabilities may offer therapeutic opportunities for disease-modifying intervention in progression-prone MPN clones. - Source: PubMed
Abdelgawwad El-Sehrawy Amr Ali MohamedAl-Khreisat Mutaz JamalKubaev AzizRajapov AdilbekIsmael Sajida HusseinAlhasso BahjatKaur IrwanjotBainsal Neeraj - FLT3-ITD mutations in acute myeloid leukemias (AMLs) cause ligand-independent signaling. One way signaling pathways potently and immediately influence cell fates is by phosphorylating key fate-determining proteins to trigger their proteolysis. We investigated the master transcription factor (MTF) driver of granulo-monocytic lineage-fates, CEBPA, for regulation by this mechanism because we found high CEBPA mRNA but little CEBPA protein in versus -wildtype AML cells, and inhibiting FLT3-ITD signaling with tyrosine kinase inhibitors (TKI) rapidly rescued CEBPA protein. Mass spectrometry revealed that CEBPA interacts with major ubiquitin-proteasome pathway (UPP) components: the ubiquitin-ligase UHRF1 and the deubiquitinase USP7. TKI treatment decreased the phosphorylation of CEBPA (Ser21) and USP7 (Ser18) alongside shifts in CEBPA interactions from degradative UHRF1 to protective USP7, stabilizing CEBPA and activating differentiation. Similarly, TKIs and UPP inhibitors stabilized the USP7 client p53, triggering apoptosis specifically in FLT3-ITD cells. Notably, UPP inhibitors (such as bortezomib) successfully stabilized CEBPA and p53 even in TKI-resistant cells. Because FLT3-ITD signaling functionally suppresses CEBPA and p53, genetic mutations in or were mutually exclusive with FLT3-ITD in clinical series. In summary, FLT3-ITD drives the UPP-mediated destruction of CEBPA and p53, positioning UPP inhibitors as promising therapeutic candidates acting downstream of TKIs. - Source: PubMed
Publication date: 2026/07/30
Saunthararajah YogenGu XiaorongBiswas SudiptaZahran ZeinabBae SongaBalusu RameshJha BabalMaciejewski Jaroslaw