Ask about this productRelated genes to: MAPK3 antibody
- Gene:
- MAPK3 NIH gene
- Name:
- mitogen-activated protein kinase 3
- Previous symbol:
- PRKM3
- Synonyms:
- ERK1, p44mapk, p44erk1
- Chromosome:
- 16p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1993-11-05
- Date modifiied:
- 2015-09-03
Related products to: MAPK3 antibody
Related articles to: MAPK3 antibody
- Pancreatic cancer is a major cause of death and one of the most challenging types of cancer which responds poorly to conventional chemotherapy and has limited therapeutic options. The scenario highlights the urgent need for the development of newer multi-targeting anticancer drugs for pancreatic cancers with higher potency, selectivity and safety profiles. The proposed research was focused on revealing the anticancer potential and mechanistic involvement of naturally occurring sesquiterpenoid nootkatone against pancreatic cancer through an integrative in silico approach. Network pharmacology and systems biology approaches were applied to identify common therapeutic targets for nootkatone that were pathophysiologically associated with the progression of pancreatic cancer. Protein-protein interaction (PPI), Gene Ontology (GO), and KEGG enrichment analyses were executed to validate the target's involvement in the pathophysiology of pancreatic cancer. Molecular docking and dynamics simulations were performed to reveal the binding potential and interactions of the nootkatone with the shortlisted anticancer targets, followed by density functional theory (DFT) analysis, ADMET prediction, and clinical relevance assessment to confirm its electrochemical and physicochemical involvement. A total of 27 overlapping targets were identified with AKT1, MAPK3, IL1β, and COX-2 revealed as the four hub target genes for nootkatone by network pharmacology. Enrichment analyses confirmed the significant involvement of PD-L1/PD-1 immune checkpoint, PI3K-AKT, MAPK, and inflammatory signaling pathways (FDR < 0.05) in the progression of pancreatic cancer. Docking analyses revealed that nootkatone has binding affinity for its targets, especially for MAPK3/ERK1 (- 8.03 kcal/mol) and AKT1 (- 7.35 kcal/mol). MD simulation over 100 ns demonstrated the stable protein-ligand complexes. DFT calculations showed a HOMO-LUMO energy gap of 2.868 eV, indicating moderate chemical reactivity and stability. Nootkatone was found to exert stronger and more stable binding against all four concerned anticancer targets with impressive electrochemical properties. ADMET predictions suggested favourable drug-likeness and Pharmacokinetics. Nootkatone can be a potential multi-targeting agent with anticancer and immunomodulatory properties by modulating the PD-L1/PD-1 immune checkpoint and signalling pathways associated with pancreatic cancer progression. However, these findings are based on in silico analyses and require further validation through in vitro and in vivo experimental studies to develop new plant-based anticancer therapeutics for pancreatic cancer. - Source: PubMed
Publication date: 2026/05/01
Goel KaranSingh Thakur GurjeetMujwar Somdutt - Congenital aniridia, a rare disorder caused by PAX6 haploinsufficiency, is characterized by progressive, vision-threatening aniridia-associated keratopathy (AAK) with limbal epithelial dysfunction and chronic inflammation. Downregulation of fatty acid binding protein 5 (FABP5) has been reported in conjunctival cells of congenital aniridia patients and in limbal epithelial cells (LECs) of the PAX6 siRNA knockdown model. We aimed to investigate the effects of FABP5 deficiency on LECs gene expression, without or with inflammatory stimuli. To achieve FABP5 knockdown, human primary LECs were transfected with FABP5 siRNA, using Lipofectamine 2000. Inflammation was induced 48 hours after transfection by incubating cells with 2 µg/mL lipopolysaccharides (LPS) or 1 ng/ml IL-1β. Thereafter, gene and protein levels were examined using qPCR, Western blot and ELISA. Significant downregulation of PAX6, KRT3 and MMP2 and upregulation of KRT12 mRNA level was observed upon FABP5 knockdown (p ≤ 0.022). Under inflammatory conditions (IL-1β or LPS treatment), FABP5 knockdown led to reduced PAX6, FOSL2, IL-6, PTGES2, KRT3, MAPK3 and MMP2 (p ≤ 0.048) and increased VEGFα and CRABP2 mRNA expression levels compared to control LECs (p ≤ 0.034). Following FABP5 knockdown, reduced PAX6, IL-6 and KRT3 protein levels were confirmed in absence of inflammatory stimuli and in cells treated with IL-1β (p ≤ 0.034). Our results suggest a novel role of FABP5 protein in AAK progression by controlling expression levels of genes and proteins involved in LEC differentiation. In addition, under inflammatory conditions, FABP5 deficiency affects key transcription factors (PAX6, FOSL2), genes regulating LEC migration, differentiation and cell maintenance (KRT3, VEGFα, MAPK3, CRABP2), and genes involved in inflammation (IL-6, PTGES2). - Source: PubMed
Publication date: 2026/04/28
Amini MaryamHsu Shao-LunStachon TanjaLi ZhenChai NingFries Fabian NSeitz BertholdKundu SwarnaliSuiwal ShwetaSzentmáry Nóra - Hypertensive Nephropathy (HN) is a severe complication of hypertension characterized by progressive renal fibrosis, which current treatments fail to halt. Huanglian Jiedu Decoction (HLJDD), a classic traditional Chinese medicine (TCM) renowned for its "heat-clearing, detoxifying" and anti-inflammatory properties, is widely used against hypertension and associated target organ damage. Thus, its potential therapeutic mechanisms against HN warrant in-depth investigation. - Source: PubMed
Publication date: 2026/04/24
Wang NingYang SiyuanLi ChangxuanWang ZhiyingMa YuanzhengLu WujinGuo MengXue YumengWu FujiaZhang MeijuanZhao YanranZhang WenjunLi ShanliangYue Guihua - Tributyl citrate (TBC), a widely used substitute for phthalate plasticizers, has shown increasing environmental accumulation, raising concerns about its potential human health risks. However, its toxicological effects, particularly regarding gastrointestinal disease progression, remain largely unexplored. In this study, animal experiments first demonstrated that TBC aggravates colonic inflammation in a mouse model of microplastic-induced colitis. Computational toxicology analysis further predicted TBC to possess potential carcinogenic properties, suggesting its role in promoting colitis-associated carcinogenesis. Using integrated bioinformatics approaches, we combined network toxicology, molecular docking, and molecular dynamics simulations to identify the putative toxicological targets and molecular pathways involved in TBC-induced inflammation-to-cancer transition. A total of 299 TBC-related targets were identified from multilevel databases, and 13 core targets were highlighted through STRING and Cytoscape analyses, including AKT2, MAPK1, MAPK3, HSP90AA1, PIK3CD, BCL2, PIK3R1, PIK3CB, ESR1, CASP3, KRAS, and ERBB2. GO and KEGG enrichment analyses indicated that TBC may drive carcinogenic progression via pathways associated with oxidative stress and inflammatory responses. Molecular docking and dynamics simulations validated the stable interactions between TBC and key targets. To further confirm TBC's role in colitis-associated tumorigenesis, we employed an AOM/DSS-induced colorectal cancer mouse model and found that TBC significantly exacerbated both intestinal inflammation and tumor formation. Transcriptomic analysis further validated the enrichment of ROS-mediated chemical carcinogenesis pathways and revealed that intestinal barrier disruption may also be a critical contributor to TBC-mediated cancer progression. Collectively, this study provides a theoretical basis for understanding the molecular mechanisms by which TBC aggravates inflammation-associated colorectal cancer, and offers a framework for risk assessment and regulatory strategies addressing plasticizer exposure in digestive health. - Source: PubMed
Publication date: 2025/10/08
Chen HaosongCheng YixianZhou YaoFu RuiJia JianguangZhang ShuyuanChen JunjieCao HaikunZhang PengGeng QilongGu JinghuaChen BoHan WenxiuXiong MaomingLi TingCao Guodong - Lung adenocarcinoma (LUAD), the most common type of non-small cell lung cancer (NSCLC), requires multi-targeted therapies to overcome resistance mechanisms and reduce toxicity. Herein, we synthesize and characterize a new sulfonyl-bridged bis(1,3,4-selenadiazole) derivative (BISDA) containing four pharmacophores that potently inhibits LUAD cell proliferation. BISDA displayed 48-h IC of 2.609 µg mL in A549 cells, decreased viability compared to controls, and was less toxic than cisplatin while inducing apoptosis, G2/M cell cycle arrest, and inhibiting cancer cell migration. BISDA remodels the redox environment by reducing glutathione peroxidase activity, and increasing intracellular glutathione levels, leading to increased PD-1 and reduced IFN-γ expression. It further downregulated prominent oncogenic drivers, EGFR, AKT1, MAPK3, mTOR, TGF β, HSP60, HSP70 and HSP90, targeting proliferation and survival with stress response in the context of metastasis. Principal component analysis showed that BISDA reprogrammed signaling through decoupling of the EGFR-mTOR axis from the TGFβ-AKT1-MAPK3-HSP90 cluster, indicative of a global rewiring of pathways. These results suggest that BISDA may serve as a multifaceted inhibitor for treating LUAD, acting in an antiproliferative capacity through apoptosis induction while also preventing signaling pathways associated with resistance. - Source: PubMed
Publication date: 2026/04/16
El-Fattah Wesam AbdGuesmi AhlemBen Hamadi NaoufelSayed Abdelwahed REl-Reedy Ahmed A MHafez Hani SElshaarawy Reda F MHassan Soha A