MDM2 (phospho-Ser166) Antibody
- Known as:
- MDM2 (phosphorilated-Ser166) Antibody
- Catalog number:
- abx000146
- Product Quantity:
- EUR
- Category:
- -
- Supplier:
- Abbexa
- Gene target:
- MDM2 (phospho-Ser166) Antibody
Related genes to: MDM2 (phospho-Ser166) Antibody
- Gene:
- MDM2 NIH gene
- Name:
- MDM2 proto-oncogene
- Previous symbol:
- -
- Synonyms:
- HDM2, MGC5370
- Chromosome:
- 12q15
- Locus Type:
- gene with protein product
- Date approved:
- 1993-12-10
- Date modifiied:
- 2017-12-01
Related products to: MDM2 (phospho-Ser166) Antibody
Related articles to: MDM2 (phospho-Ser166) Antibody
- Tyrosine kinase inhibitors (TKI) are frontline therapies for oncogene-addicted cancers, yet metabolic rewiring frequently drives acquired resistance. Here, we identify a mitochondrial trafficking mechanism that regulates oxidative phosphorylation (OXPHOS) dependence in TKI-resistant tumours. Using resistant cell models and patient-derived materials, we demonstrate that OXPHOS activation is regulated by an AKT-driven, competitive interaction between mitochondrial MDM2 and the mitochondrial transcription factor TFAM at mitochondrial DNA (mtDNA). Mechanistically, adaptive AKT activation promotes cytosolic redistribution of MDM2 with reciprocal accumulation of TFAM in mitochondrial, enhancing mtDNA transcription and OXPHOS activity. To validate this mitochondrial-cytosolic exchange, we develop a quantitative, high-resolution imaging approach to map MDM2 and TFAM localization. In a TKI-resistant clinical cohort (n = 76), we revealed a positive correlation between AKT activation, MDM2 phosphorylation and TFAM mitochondrial trafficking, defining a spatial, subcellular biomarker signature of metabolically reprogrammed TKI resistance. Pharmacologic disruption of the AKT-MDM2-TFAM signaling axis reverse TKI resistance, linking mitochondrial genome regulation to therapy resistance and suggesting a metabolic vulnerability for combinatorial targeting. - Source: PubMed
Publication date: 2026/04/16
Eu Jie QingBinte Mohamed Salleh Nur AfiqahHirpara JayshreeOhi NaotoTakaki Emiri OmoriTan Tuan ZeaSeet Ju EeHue Susan Swee-ShanChan Shu JunLim Dorothy Xi YueWang LingzhiWong Regina Tong XinAli AzharLim Yaw ChynGoh Boon-CherKong Li RenPervaiz ShazibWong Andrea LA - With the widespread distribution and increasing detection levels of Bisphenol A bis (diphenylphosphate) (BDP) in environment, toxicity risk assessment on BDP has become indispensable issue. So far, available toxicological information about BDP is still limited. In this study, a hormesis-like effect of BDP in HepG2 cells was observed and potential mechanism was investigated. BDP (<2μM) promoted proliferation ability and stimulated the migration and invasion ability of HepG2 cells as evidenced by increased viability, accelerated colony formation, hasted scratch healing, down-regulated E-cadherin, and up-regulated matrix metalloproteinase (MMP-9) and mouse double minute 2 homolog (MDM2) proteins. However, high doses of BDP (>20μM) exhibited completely opposite effects to that of lower dose. Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) axis was involved in the stimulating effect induced by 0.2μM of BDP through activation of the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway and extracellular regulated protein kinases (ERK)/p38 mitogen activated protein kinase (MAPK) cascades, and there was a bidirectional regulation between the latter two pathways. Our results demonstrated the network of VEGF/VEGFR, Akt/mTOR, and ERK/p38 MAPK pathways involving in BDP-induced stimulating effect on proliferation, migration and invasion ability of HepG2 cells, which providing a novel insight on toxicology risk assessment of BDP. - Source: PubMed
Publication date: 2026/04/14
An JingYi YutingLi NaLin MiaoZhong YufangRen GuofaShang Yu - Characterization of molecular features of cholangiocarcinoma (CCA) has questioned the traditional, anatomy-based classification scheme and has alternatively suggested biology-based classifications. Intrahepatic CCA has been classified into small-duct and large-duct types, and the latter is histologically and molecularly almost identical to perihilar CCA. Although distal and perihilar CCA have been classified together, they have different molecular abnormalities, with MDM2 amplification observed in 15% of perihilar CCA cases but in none of the distal CCA cases. FGFR2 and IDH1 are two main drug targets in small-duct intrahepatic CCA, and mismatch repair (MMR) deficiency is most common in small-duct intrahepatic CCA. In contrast, HER2 is a promising target for extrahepatic CCA and gallbladder cancer, as HER2 overexpression is seen in 17%-30% of cases. Classification of intrahepatic CCA is often challenging on biopsy specimens; however, recognition of pitfalls (e.g., hybrid morphology) will help avoid misclassification. Staining for ancillary markers, including CRP, albumin-ISH, and S100P, is also useful. Accurate distinction between distal CCA and pancreatic head cancer has become increasingly important, particularly in unresectable or borderline resectable cases, as systemic treatment strategies differ between these entities. Although these two neoplasms share many morphological and immunohistochemical features, the presence of clear or foamy cancer cells in biopsy specimens is uncommon in dCCA and may favour pancreatic ductal carcinoma. - Source: PubMed
Publication date: 2026/04/16
Zen Yoh - The transcription factor p53, often called the "guardian of the genome," is critical for preserving genomic integrity. Mutations in the TP53 gene are found in approximately half of all human malignancies, including breast, colon, lung, liver, prostate, bladder, and skin cancers. p53 is activated by a wide range of cellular stress signals and orchestrates specific cellular responses based on the context and nature of the stress. As a tumor suppressor, p53 controls cancer initiation and progression by regulating cell cycle arrest, apoptosis, senescence, and DNA repair. Beyond its classical role in genome surveillance, p53 is now recognized as a dynamic signaling hub whose functions can be therapeutically modulated in cancer. Natural products derived from medicinal plants represent a rich source for discovering and developing novel therapeutic and preventive agents against cancer. Several natural compounds have been reported to target mutant p53 in cancer cells, offering a potentially effective strategy for modulating the p53 signaling pathway. This review highlights recent advances in identifying and developing anticancer natural products that modulate the expression or activity of the p53 tumor suppressor gene for cancer treatment and prevention. - Source: PubMed
Publication date: 2026/04/16
Nandi SudeshnaNaskar ArghyaKhatua SomanjanaAcharya KrishnenduBüsselberg DietrichHerrera-Bravo JesúsArancibia-Diaz AlejandraSetzer William NRotariu Lia SandaDragunescu Anca AnetaButnariu MonicaSharifi-Rad Javad - MDM2 is an E3 ubiquitin ligase that promotes p53 tumor suppressor degradation and has emerged as a therapeutic target in the treatment of wild-type (wt) TP53 tumors. In acute myeloid leukemia (AML), TP53 mutations are infrequent (15-20%), but wt-p53 is often inactivated through overexpression of MDM2. Thus, MDM2 inhibitors are currently in clinical trials for AML. However, p53 stabilization with inhibitors upregulates MDM2, which limits their clinical efficacy. Proteolysis-targeting chimeric (PROTAC) molecules that degrade MDM2 may overcome this feedback. MD-265 is a PROTAC that recruits CRBN, degrades MDM2, restores p53 and induces apoptosis. We tested MD-265 in ex vivo cultures of 105 primary leukemic stem cells (LSCs). The median cytotoxic IC for MD-265 was 16 nM, median IC for MI-1061 was 150-fold higher. LSCs with IC > 1 µM were classified as MD-265 resistant and harbored mutations in TP53. Normal hematopoietic stem cells showed 100-fold higher IC (818 nM) than LSCs. AML patient-derived xenograft (PDX) models in NSG-SGM3 mice were treated with MD-265 or an oral MDM2 inhibitor. In PDX models, MD-265 was not toxic and prolonged survival. MD-265 is a potent and specific MDM2 degrader with broad pre-clinical activity and a promising drug candidate for the treatment of leukemias. - Source: PubMed
Publication date: 2026/04/15
Kandarpa MalathiPeterson Luke FPotu HarishRamappan MeghaLiu YihongPolk AveryWang ShaomengTalpaz Moshe