MPG

Last update 08 May 2025

Basic Info

Synonyms

3-alkyladenine DNA glycosylase, 3-methyladenine DNA glycosidase, AAG

+ [8]

Introduction

Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, and 7-methylguanine from the damaged DNA polymer formed by alkylation lesions.

100 Clinical Results associated with MPG

100 Translational Medicine associated with MPG

0 Patents (Medical) associated with MPG

1,309

Literatures (Medical) associated with MPG

31 Dec 2025·Annals of Medicine

Identification of ALDH7A1 as a DNA-methylation-driven gene in lung squamous cell carcinoma

Article

Author: He, Jinxian ; Zhang, Liang ; Yu, Kaizhong ; Shen, Weiyu ; Chen, Tian ; Liang, Gaofeng

BACKGROUNDDeoxyribose nucleic acid (DNA) methylation is an important epigenetic modification that plays an important role in the occurrence and development of tumors. Identifying key methylation-driven genes that affect the prognosis of lung squamous cell carcinoma (LUSC) can provide direction for targeted therapy research.METHODS AND RESULTSMethylation and RNA-seq data were downloaded from The Cancer Genome Atlas (TCGA). The MethylMix package was used to integrate and analyze the methylation and gene expression data from TCGA, and the LUSC dataset (GSE37745) was downloaded from GEO for validation. Forty-five DNA-methylation-driven genes (MDGs) were obtained, and 3 genes (TRIM61, SMIM22, and ALDH7A1) were significantly associated with survival by using univariate and multivariate Cox regression. A risk model was constructed. KM analysis showed that patients with high-risk scores had poor survival. A nomination plot for prognosis prediction of LUSC patients was constructed, which showed a good predictive efficiency for tumor prognosis. The high expression of ALDH7A1 was an independent risk factor for poor prognosis in LUSC. The expression of ALDH7A1 in LUSC was negatively correlated with its methylation status (COR = -0.655). GSEA analysis showed that high expression of ALDH7A1 could activate multiple signaling pathways (JAK-STAT signaling pathway and mTOR signaling pathway). In vitro cell experiments confirmed that in LUSC, silencing ALDH7A1 could inhibit tumor progression, while overexpression of ALDH7A1 could promote tumor progression.CONCLUSIONOur results indicated that ALDH7A1, a newly discovered MDG in LUSC, could act as an independent prognostic factor for OS in LUSC, with the potential to become a potential target for LUSC diagnosis and treatment. High expression of ALDH7A1 in LUSC could promote the occurrence and development of tumors. Signaling pathways, such as JAK-STAT and mTOR signaling pathways, might regulate the high expression of ALDH7A1.

01 Dec 2025·Cancer Chemotherapy and Pharmacology

Pharmacokinetics, metabolism, and excretion of [14C]-valemetostat in healthy male participants, and in vitro plasma protein binding

Article

Author: Shimizu, Takako ; Tachibana, Masaya ; Abutarif, Malaz A ; Kazui, Miho ; Inaba, Shinichi ; Craveiro, Thuy Vu ; Ikeda, Tomoko ; Siebers, Nicholas

INTRODUCTIONValemetostat tosylate (valemetostat) is an oral, selective, dual inhibitor of enhancer of zeste homolog (EZH)2 and EZH1. This article reports findings on the mass balance and pharmacokinetics of valemetostat in a phase I study; valemetostat metabolite identification in plasma, urine, and fecal samples; and plasma-protein-binding of valemetostat in vitro.METHODSEight healthy participants received a single 200-mg oral dose of [¹⁴C]-valemetostat under fasting conditions. Blood, urine, and feces samples were collected to determine total radioactivity and/or unchanged valemetostat, and for metabolite identification. The binding of valemetostat 600-10,000 ng/mL to plasma, 4% human serum albumin (HSA), and 0.1% alpha-1-acid glycoprotein (AAG) was assessed in vitro.RESULTSMean cumulative recovery of administered radioactivity was 95.3% by 360 h post-dose, with a mean recovery of 15.6% in urine and 79.8% in feces. Valemetostat accounted for the most radioactivity in the excreta, at 10% and 64.9% of the administered dose in the urine and feces, respectively. CALZ-1809a was the most abundant metabolite, present in all biological samples, and accounted for 5.6% of total radioactivity in the feces. Valemetostat was minimally associated with red blood cells, with a blood-to-plasma total radioactivity ratio of 0.54. In vitro, valemetostat was highly plasma-bound (> 94%) at clinically relevant concentrations, with a higher affinity to AAG than to HSA.CONCLUSIONValemetostat was rapidly absorbed into the systemic circulation, mainly excreted via the biliary/fecal route, primarily metabolized by CYP3A enzymes to CALZ-1809a, and highly bound to plasma proteins, with a greater affinity to AAG than HSA in vitro.

01 May 2025·Diabetes & Metabolism

Screening for autoimmune atrophic gastritis by serum gastrin measurement in subjects with type 1 diabetes

Article

Author: Larger, Etienne ; Pacheco, Aude ; Mallone, Roberto ; Goulvestre, Claire ; Alexandre-Heymann, Laure ; Dubois-Laforgue, Danièle ; Diedisheim, Marc

INTRODUCTIONDespite associated risk of anemia and gastric cancer, screening for autoimmune atrophic gastritis (AAG) is underperformed in subjects with type 1 diabetes mellitus (T1DM). We measured the predictive value of serum gastrin as a biomarker of gastric atrophy in subjects with T1DM and parietal cell autoantibodies (PCA).SUBJECTS AND METHODSPCA measurements were retrospectively retrieved in 1,425 consecutive subjects with T1DM between 2014 and 2018. Screening for AAG was conducted in PCA+ subjects by measuring blood counts, serum ferritin, vitamin B12 and gastrin; and by performing gastroduodenal fibroscopy, with fundic biopsies for histology and Helicobacter pylori. The performance of blood biomarkers of gastric atrophy was analyzed in comparison with the histopathological gold standard.RESULTSPCA were found in 185/1,425 subjects (13 %). PCA positivity was associated with female sex, older age, longer T1DM duration, and co-occurrence of anti-GAD and anti-thyroperoxydase autoantibodies. Of the 185 PCA+ subjects, 122 (66 %) participated in screening. AAG was found in 69/122 (57 %) subjects and Helicobacter pylori infection in 20/122 (16 %). Compared to PCA+ subjects without gastric atrophy, those with gastric atrophy had more frequently iron deficiency (65 % vs. 18 %, P < 0.0001), and/or vitamin B12 deficiency (57 % vs. 7 %, P < 0.0001); 44/69 (64 %) presented a pre-tumoral lesion and 6 % a tumor. Using a cut-off of 1.2-fold above the upper normal limit, serum gastrin concentration displayed 91 % sensitivity and 82 % specificity at predicting gastric atrophy.CONCLUSIONIn subjects with T1DM and PCA, serum gastrin is a reliable biomarker of gastric atrophy that can be used to select subjects requiring gastroduodenal fibroscopy.

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