ZAP70 Antibody Phospho (pY292)
- Known as:
- ZAP70 Antibody Phospho (pY292)
- Catalog number:
- AJ1824c
- Product Quantity:
- 100ul
- Category:
- -
- Supplier:
- Abgen
- Gene target:
- ZAP70 Antibody Phospho (pY292)
Related genes to: ZAP70 Antibody Phospho (pY292)
- Gene:
- ZAP70 NIH gene
- Name:
- zeta chain of T cell receptor associated protein kinase 70
- Previous symbol:
- SRK
- Synonyms:
- ZAP-70, STD
- Chromosome:
- 2q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1995-05-16
- Date modifiied:
- 2019-04-23
Related products to: ZAP70 Antibody Phospho (pY292)
Related articles to: ZAP70 Antibody Phospho (pY292)
- CEACAM1 homodimerization mediates tumor immune evasion, presenting a compelling target to overcome resistance to PD-1 blockade. However, defining a precise structural and pharmacological blueprint for CEACAM1 targeting has remained challenging. Here, we report the discovery and comprehensive preclinical characterization of MG1124, a highly specific, fully human monoclonal antibody targeting the CEACAM1 IgV domain. X-ray crystallographic analysis at a 1.8 Å resolution revealed that MG1124 binds the homodimerization interface with robust affinity (KD = 37.8 nM), physically disrupting both homophilic and heterophilic inhibitory interactions without cross-reacting with highly homologous CEACAM members. This targeted structural blockade effectively reversed CEACAM1-mediated suppression of T-cell receptor signaling, restoring ZAP70 phosphorylation and IL-2 production, while potently enhancing NK- and CD8⁺ T-cell cytotoxicity against CEACAM1-high tumor cells. In vivo, MG1124 reprogrammed the tumor immune microenvironment by increasing effector cytokine production in human CEACAM1 knock-in mice. It also demonstrated robust tumor growth inhibition in humanized non-small cell lung cancer (NSCLC) patient-derived xenograft (PDX) models, synergizing profoundly with PD-1 blockade. Furthermore, multiplex immunofluorescence profiling of human NSCLC tissues confirmed robust CEACAM1 expression across tumor and immune compartments, reinforcing its translational validity. Finally, MG1124 exhibited a highly favorable, drug-like pharmacokinetic profile in cynomolgus monkeys, characterized by prolonged systemic exposure and low clearance. By defining the structural basis of CEACAM1 blockade and demonstrating translational efficacy, this study introduces MG1124 as a novel therapeutic antibody, providing a robust pharmacological foundation for cancer immunotherapy. - Source: PubMed
Publication date: 2026/08/27
Lee Jae-ChulOh MiyoungNam Hye-MiCho Hyun-JungKim Jae HwanCho Byoung ChulKim SeonghoonOh Byung-HaLee Chang-Woo - Antigen 85B (Ag85B), an immunodominant protein secreted by (Mtb), induces robust T-cell-mediated immunity in host cells. Previous studies have demonstrated that recombinant BCG strains overexpressing Ag85B (BCG85B) confer significant protection against tuberculosis in mouse models. This study hypothesized that enhanced protection by recombinant BCG85B results from modulation of host immune gene expression by the Ag85B antigen. To test this, RNA-seq analysis was performed on splenocytes from mice immunized with the wild-type BCG (BCG-WT) and BCG85B strains. Differentially expressed genes (DEGs) in the splenocytes of BCG85B-immunized mice indicated upregulation of immune-related KEGG pathways, including Th1/Th2 and Th17 differentiation, NF-kappa B signaling, and cytokine-cytokine receptor interactions, as well as Gene Ontology (GO) processes such as immune response activation, α-β T cell activation, T-cell production and differentiation, IL-15 mediated signaling, and cytokine-mediated signaling pathways and down regulation of metabolic and digestive processes. Additionally, transcription factor (TF) and protein-protein interaction (PPI) analyses confirmed upregulation of genes involved in T cell receptor signaling and immune activation (, , , , , , and ) in splenocytes from BCG85B-immunized mice. Collectively, these findings indicate that Ag85B overexpression enhances adaptive immune activation and reprograms cellular metabolic pathways, thereby increasing vaccine efficacy. - Source: PubMed
Publication date: 2026/08/12
Chauhan VivekKumar RakeshVeerapandian RajaRamos Enrique IJagannath ChinnaswamyGadad Shrikanth SDhandayuthapani Subramanian - Indolo[2,3-]quinoxalines, along with their -substituted derivatives, exhibit pronounced anticancer activity, although the mechanisms of their biological action may vary. Herein, a panel of sixty-five 6-(2-aminoethyl)-6-indolo[2,3-]quinoxaline derivatives comprising eight series with distinct amine moieties connected to the tetracyclic indoloquinoxaline core via a dimethylene linker was evaluated as drug-like candidates for kinase binding and cytotoxic activity. The ADME (Absorption, Distribution, Metabolism, and Excretion) properties of the compounds included in this set were preliminarily determined using the SwissADME tool. Analysis revealed that the library of quinoxaline derivatives largely complies with the drug-likeness rule for kinase-targeted compounds. As part of the biological screening, the compounds were initially tested on two cell lines MonoMac-6 and THP-1 (both derived from patients with acute monocytic leukemia) using sunitinib, a known antitumor agent acting as a multi-target receptor tyrosine kinase inhibitor, as a reference compound. Compound , which demonstrated the highest activity in the cytotoxicity analysis (IC = 1.9 and 3.5 μM for the MonoMac-6 and THP-1 cell lines, respectively), was screened using the Eurofins DiscoverX scanEDGE panel, comprising 97 distinct kinases representing all known kinase families. Subsequently, the compound was tested using the Eurofins DiscoverX scanTK™ panel, covering 135 distinct receptor and non-receptor tyrosine kinases. Based on initial screening results, compound exhibits relatively high binding activity against fourteen tyrosine kinases, including TYK2, ZAP70, eight mutant forms of ABL1, two mutant forms of FLT3, and one mutant form of ALK, and demonstrates relatively high binding selectivity with respect to non-mutant tyrosine kinases (S-score: 0.024). Secondary screening of nine selected analogs of compound led to the identification of compound , which demonstrates relatively high binding affinity for FLT3 (D835V) (K = 0.41 μM). Molecular modeling suggested modes of binding interaction of the compounds and in the FLT3 (D835V) catalytic site. Our results demonstrate that 6-(2-aminoethyl)-6-indolo[2,3-]quinoxaline derivatives could be potential candidates for developing anticancer drugs. - Source: PubMed
Publication date: 2026/08/12
Schepetkin Igor AUvarov Alexander VEvriinov Egor AKhlebnikov Andrei I - Hepatocellular carcinoma (HCC) frequently demonstrates resistance to immunotherapeutic interventions, a phenomenon largely linked to mechanisms of immune escape. Among the modulators of the tumor microenvironment, SPARC (Secreted Protein Acidic and Rich in Cysteine), a matricellular glycoprotein, has been associated with diverse oncogenic processes in multiple cancer types. However, the contribution of SPARC to immune regulation through CD276 signaling remains insufficiently characterized. To clarify this mechanism, we employed the murine Hepa1-6 hepatoma cell line established from C57BL/6 mice. Functional studies were carried out by genetically altering the expression of SPARC and CD276, followed by comprehensive assessments including Western blot analysis, polymerase chain reaction, flow cytometry, and in vivo tumorigenicity assays. Overexpression of SPARC in HCC cells led to increased CD276 levels through activation of the p65/c-Myc axis, which also promoted cancer cell stemness. This upregulation impaired the response to immune checkpoint blockade (ICB) therapy, as evidenced by reduced infiltration and activation of CD8 + T cells within the tumor microenvironment. Additionally, increased SPARC-induced CD276 expression diminished T-cell activation and proliferation, marked by decreased IFN-γ production and reduced phosphorylation of ZAP70, a key T-cell signaling molecule. Our findings underscore the critical role of SPARC in upregulating CD276 in HCC, which contributes to immune suppression and resistance to ICB therapy. - Source: PubMed
Tang MengyingLiu Jing - Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by antibody-mediated platelet destruction and impaired regulatory T-cell (Treg) function, yet its molecular basis remains poorly defined. Here, we show that CD4+ naive T cells from patients with ITP exhibit diminished T-cell receptor (TCR) signaling and impaired in vitro Treg induction relative to healthy controls. RNA-sequencing revealed widespread alternative splicing dysregulation, most notably exon 8 skipping in LCK, a kinase central to TCR signaling and Treg differentiation. Using an LCK minigene combined with RNA pull-down mass spectrometry and RNA immunoprecipitation assays, we identified the splicing factor SRSF1 as a direct upstream regulator of LCK exon 8 skipping. Notably, SRSF1 expression was reduced in CD4+ naive T cells from ITP patients, and its overexpression restored in vitro Treg induction capacity. Antisense oligonucleotide (ASO)-mediated blockade of SRSF1 binding to LCK enhanced exon 8 skipping and attenuated TCR activation in Jurkat cells. Although murine Lck lacks the human-specific recursive splicing sites required for exon 8 exclusion, adoptive transfer of CD4+ naive T cells expressing the exon 8-skipped murine Lck into CD61-knockout mice significantly reduced Treg proportions and platelet counts in an active ITP model. Mechanistically, Jurkat cells engineered to express only the exon 8-skipped LCK variant showed markedly reduced binding to ZAP70 and CD3ζ, which may partly account for the attenuated TCR signaling and downstream FOXP3 induction. Together, these findings define a novel SRSF1-LCK splicing axis that may regulate Treg development in ITP. - Source: PubMed
Publication date: 2026/08/17
Hu XiangLeng ShaoqiuLiu YanZhao RuxiaLiu XinyueLi JuZhang ChengMeng CaiyunLiu HaoranZhang YanqiLi ChaoyangWang YuxinFeng QiJiang NanXu ShuqianWang ShuwenPeng Jun