DEPC TREATED WATER
- Known as:
- DEPC TREATED WATER
- Catalog number:
- ec-6251ltr
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- AGTC National Diagnostics
- Gene target:
- DEPC TREATED WATER
Related genes to: DEPC TREATED WATER
- Gene:
- ALKBH3 NIH gene
- Name:
- alkB homolog 3, alpha-ketoglutaratedependent dioxygenase
- Previous symbol:
- -
- Synonyms:
- DEPC-1
- Chromosome:
- 11p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 2006-02-09
- Date modifiied:
- 2018-05-03
Related products to: DEPC TREATED WATER
Related articles to: DEPC TREATED WATER
- Glioblastoma (GBM) is a highly aggressive, poor-prognosis brain tumor classified as WHO grade IV, for which effective treatments remain limited. Although AlkB homolog 3 (ALKBH3), a demethylase for 1-methyladenosine (m1A) and 3-methylcytidine (m3C) in DNA and RNA, has been implicated in cancer cell proliferation, its functional role in GBM remains unclear. We aimed to characterize the role of ALKBH3 in GBM and develop and evaluate a patented ALKBH3 inhibitor, HUHS199, to identify its molecular targets and therapeutic potential. We found that ALKBH3 was highly expressed in clinical GBM specimens; its knockdown inhibited GBM cell proliferation. HUHS199 inhibited GBM cell proliferation in a dose-dependent manner, induced G1 phase cell cycle arrest, and increased m1A levels in RNA. Furthermore, RNA immunoprecipitation-microarray analysis using an anti-m1A antibody identified growth arrest and DNA-damage-inducible protein GADD45 alpha (GADD45A) mRNA as a target of ALKBH3-mediated demethylation. These findings suggest that ALKBH3 promotes GBM cell proliferation via m1A demethylation of GADD45A mRNA. Collectively, this study highlights the therapeutic potential of ALKBH3 inhibition and presents HUHS199 as a first-in-class candidate for GBM treatment. - Source: PubMed
Yamada ManamiHase HiroakiKitamura HonokaMorie ToshiyaAoi ShuntaroUeda YukoKitae KaoriFurukawa TatsuhikoHiga NayutaHanaya RyosukeTsujikawa Kazutake - Diabetic microvasculopathy is a serious diabetes complication, with diabetic retinopathy (DR) being a leading cause of blindness worldwide due to immature, leaky neovessels. Antiangiogenic therapies merely suppress neovascularization, leaving the retina oxygen-starved and prone to regrowth. Thus, therapies that stabilize aberrant neovessels are needed. We identify the RNA demethylase ALKBH3 as an epitranscriptional driver of diabetic microvasculopathy. Upregulated ALKBH3 in diabetic vascular endothelial cells promoted a pathological shift to an unstable, pro-angiogenic phenotype, disrupting blood-retinal barrier and forming immature neovessels, which impaired vision. Conversely, removing ALKBH3 protected against this. Mechanistically, ALKBH3 demethylated mRNA to increase its stability via YTHDF2. We further developed a neovasculature-targeting nanoparticle delivering the ALKBH3 inhibitor HUHS015, which normalized retinal neovascularization by simultaneously limiting growth and promoting maturation. It acted synergistically with vascular endothelial growth factor (VEGF) blockade, suggesting potential for anti-VEGF-resistant cases. Our work defines ALKBH3 as a key mediator of diabetic microvasculopathy and supports a VEGF-independent therapeutic paradigm that shifts the focus from vessel suppression to active normalization. - Source: PubMed
Publication date: 2026/08/21
Zhang Yi-ChenDing Zi-QinXu Shi-YaoChen Ji-YuChen Ming-HuiLuo Bing-QingWang YingWu Yan-YiLv Xin-YaoLiu Xing-ZhuZhao ChenLiu Qing-HuaiChen Xue - The nucleolus is a membraneless nuclear organelle formed by liquid-liquid phase separation and serves as the hub for ribosomal RNA (rRNA) transcription and ribosome assembly. Here, we identify ALKBH3, a Fe(II)/α-ketoglutarate-dependent dioxygenase, as a previously unrecognized nucleolar protein that colocalizes with the scaffold protein Nucleophosmin 1 (NPM1). Loss of ALKBH3 reduced nascent and precursor rRNA levels, impaired global protein translation, and suppressed cell proliferation. Although ALKBH3 lacked intrinsic LLPS capacity, it was recruited into NPM1 condensates via a direct interaction mediated by an N-terminal KRRRAR motif. Consistently, NPM1 knockdown diminished ALKBH3 nucleolar localization in cells, while in vitro assays demonstrated ALKBH3-NPM1 co-condensation. In zebrafish, alkbh3 knockdown decreased pre-rRNA abundance and caused dose-dependent developmental delays. Together, these findings establish ALKBH3 as an NPM1-dependent nucleolar client protein critical for rRNA biogenesis, protein synthesis, and vertebrate development. - Source: PubMed
Publication date: 2026/08/17
Ma XixiHuang YuliangJin HaoZhang RuiLiu FangzhouLin AifuZhou TianhuaXie Shanshan - The field of epitranscriptomics, an area of genetics concerning the regulation of gene expression via post-transcriptional RNA modification, is currently attracting substantial research attention. In epitranscriptomics, proteins, collectively termed writers, erasers, and readers, enter into complex interactions that contribute to modifying RNA, thereby maintaining biological homeostasis. However, abnormalities in the expression or function of these proteins can lead to the onset and progression of cancers and neuropsychiatric disorders. Using prostate cancer clinical specimens, I cloned a novel gene, prostate cancer antigen-1 (PCA-1), containing a domain similar to the 2-oxoglutarate, iron(II) [Fe(II)]-dependent oxygenase domain of the Escherichia coli AlkB protein and characterized by enzymatic activity associated with the demethylation of methylated RNA. This was accordingly designated AlkB homolog 3 (ALKBH3). I demonstrate that ALKBH3 is highly expressed in tumor cells in prostate, pancreatic, lung, and other cancers, and its activity is correlated with a poor prognosis. In addition, I developed novel compounds that inhibit the RNA demethylase activity of ALKBH3, thereby providing a basis for developing a first-in-class cancer therapeutic. I also succeeded in cloning the ALKBH8 gene. High ALKBH8 expression was also observed in bladder cancer cells. Furthermore, abnormalities in development and behavior were noted in the generated Alkbh8 knockout mice. On the basis of the experience gained from ALKBH3 drug discovery research, I have established a foundation system for supporting academic drug discovery research. In this review, I describe the pathway followed in integrating the findings of basic pharmaceutical and drug discovery research and further developments. - Source: PubMed
Tsujikawa Kazutake - Triple-negative breast cancer (TNBC) exhibits marked molecular heterogeneity, posing ongoing therapeutic challenges. Metabolic reprogramming, particularly through the Warburg effect, offers a promising therapeutic target for TNBC treatment. Data mining and machine learning identified (+)-miliusol as a promising candidate. Its direct target, eukaryotic initiation factor 3D (EIF3D), was validated through mass spectrometry-coupled cellular thermal shift assay (MS-CETSA), a biotinylated probe, and a proteolysis-targeting chimera (PROTAC) approach. EIF3D, an emerging oncoprotein and atypical translation initiation regulator, promotes tumor survival by selectively modulating protein synthesis. (+)-Miliusol demonstrates potent anti-proliferative and anti-migratory activity against TNBC in both and . Integrated proteomic and transcriptomic analyses revealed that (+)-miliusol suppresses TNBC progression through EIF3D-mediated translational regulation. Mechanistically, it disrupts the EIF3D-AlkB homolog 5 (ALKBH5)-glucose transporter type 4 (GLUT4) axis, EIF3D-HIF1 signaling, and the EIF3D-RuvB like AAA ATPase 1 (RUVBL1)--catenin pathway, thereby inhibiting glycolysis and metastasis while inducing ER stress-dependent apoptosis caspase-12 and JNK activation. Additionally, (+)-miliusol blocks EIF3D-HIF1 and EIF3D-ALKBH3 interactions, impairing ATAD2/PAK1-regulated Warburg-effect networks and triggering autophagy-associated cell death. (+)-Miliusol induces TNBC cell death by selectively suppressing translation of critical glycolytic and metastatic regulators. These findings establish EIF3D-mediated translational control as a promising therapeutic avenue for TNBC treatment. - Source: PubMed
Publication date: 2026/03/16
Zhang JinJia LinChen XiyaWu YanSun XiaohanZou LingCheng XiaolingHuang JingnanZhou HongchaoDai LingyunZhou LeHe ZhendanLiu BoHao YueYao Dahong