Ask about this productRelated genes to: CYP3A7 Blocking Peptide
- Gene:
- CYP3A7 NIH gene
- Name:
- cytochrome P450 family 3 subfamily A member 7
- Previous symbol:
- -
- Synonyms:
- CP37, P450-HFLA
- Chromosome:
- 7q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 1992-09-14
- Date modifiied:
- 2015-12-09
Related products to: CYP3A7 Blocking Peptide
Related articles to: CYP3A7 Blocking Peptide
- The interaction between the gut microbiome and drug metabolism is bidirectional and can influence the pharmacokinetics of certain drugs. In mice, the gut microbiome has been shown to influence Cyp3a11. However, evidence for microbial regulation of human cytochrome P450 3A4 (CYP3A4) is lacking. We aimed to bridge this gap by manipulating the microbiome of a humanized mouse model expressing CYP3A4, CYP3A7, pregnane X receptor and constitutive androstane receptor. Three groups of male and female humanized mice were studied: conventional (CV), germ-free (GF), and germ-free mice conventionalized (GFCV) using sex-matched pooled human fecal samples. The presence of microbiome upregulated CYP3A4 expression by 7.6-fold in male CV mice (P < .001) but downregulated CYP3A4 expression by 1.69-fold in female CV mice (P = .012) compared with GF mice. The human fecal microbiome transplant to sex-matched GF mice resulted in decreased microbial diversity (P < .05 in males and P < .01 in females) and was not effective in restoring CYP3A4 expression, suggesting complex underlying microbe-CYP3A4 interactions. We show that the hepatic CYP3A4 mRNA and protein expression were strongly correlated (R = 0.91; P = 2.6 × 10). A total of 57 bacterial species from the mouse gut microbiome were identified to be significantly correlated with CYP3A4 protein expression (P < .05). Five bile acids and no short-chain fatty acids were correlated with CYP3A4 protein expression. In summary, alterations in the gut microbiome influenced hepatic CYP3A4 in humanized mice in a sex-dependent manner, with distinct microbes strongly correlating with this regulatory pattern. SIGNIFICANCE STATEMENT: To the best of our knowledge, this study is the first to evaluate the expression of cytochrome P450 3A4 under different microbial conditions in a humanized mouse model, including conventionalization of germ-free mice using pooled sex-matched human feces. Alterations in the gut microbiome influenced hepatic cytochrome P450 3A4 in a sex-dependent manner and were strongly correlated with microbial species. - Source: PubMed
Publication date: 2026/03/26
Liem JenniferChen XinLim Joe JMao QingchengCui Julia YLin Yvonne S - Most medications administered during pregnancy will enter the fetal circulation through the placenta. The activity of placental drug-metabolizing cytochrome P450 (CYP) enzymes modulates the extent of this transfer. However, many gaps exist in understanding how CYP expression and activity vary across gestation and how placental sex influences these changes. Therefore, we aimed to characterize the expression and activity of placental CYPs throughout gestation stratified by sex. Placentas were collected from participants who provided informed consent and received care at the University of Pennsylvania hospital between 18-23.5 weeks gestational age (GA; Tri2, n=27), 20-36 weeks GA for preterm delivery (preterm, n=40), or 37 to 41 weeks GA for uncomplicated delivery (term, n=40). The DESeq2 R package was used to perform differential expression analysis of CYP gene expression. CYP2C8 and 2D6 activity was measured in vitro using established mass spectrometry assays and analyzed using Kruskal Wallis-ANOVA. Placental expression of CYP1A2, CYP2C8, CYP3A5, and CYP3A7 decreased towards the end of pregnancy, whereasCYP2C9 and CYP2D6 expression increased toward the end of pregnancy. When considering placental sex, CYP2D6 expression was lower in Tri2 vs term in males (log fold change (logFC)=-1.1123) and females (logFC=-1.3750), whereas CYP2C8 was higher in the same comparisons (male logFC=1.4940, female logFC=1.2659). In females only, CYP2D6 and CYP2C8 activity increased in term vs Tri2 placentae (P=0.0004 and P=0.0281, respectively). Consistent with this, female placental CYP2D6 and CYP2C8 activity was positively associated with gestational age (P=0.0020 and P=0.0009, respectively). Placental activity of two CYPs responsible for metabolizing 25% of drugs increases from Tri2 to term in a sex-specific manner, which may affect fetal exposure to maternally administered medications metabolized by these isoforms. - Source: PubMed
Publication date: 2026/02/10
Albetawi Saba NMeakin Ashley SLien Yu-ChinWiese Michael DSimmons Rebecca AMorrison Janna L - Lung cancer is the third most common cancer in the US with a 5-year survival rate of 17%. Non-small cell lung cancer, especially adenocarcinoma, prevails. Therefore, early detection and biomarker discovery are extremely important. This study uses deep learning to find new biomarkers for lung adenocarcinoma. RNA-Seq data from 522 samples, including 506 lung adenocarcinoma patients and 16 healthy controls, were analyzed. DEGs were identified after strict preprocessing, and deep learning algorithms predicted markers. Functional annotation, pathway, and protein interaction analyses elucidated the biological importance of DEGs. Clinical relevance was assessed by correlation with clinical parameters and survival analysis. External validation was carried out using GDAC and GEO datasets. Blood samples from 30 lung adenocarcinoma patients and 30 healthy people were analyzed by real-time PCR to validate the expression levels of key genes. Among 522 participants(506 cases, 16 controls), the mean age was 62.95 ± 15.71 years. Normalized data showed 3,513 DEGs. The deep learning model had a predictive accuracy of 98.44%, Brier score (probability MSE) = 0.0013, and AUC of 1.0. CYP3A7 had the highest effect size. ROC analysis found diagnostic genes A2M, CYP2C9, and SIRPD (Ensembl ID: 128646) with a sensitivity of 0.96. Real-time PCR showed upregulated CYP2C9, KRT14, and PECAM1 and downregulated A2M in patients compared to controls(P < 0.001). Bioinformatics-identified genes are potential markers for early lung adenocarcinoma detection and management. RT-PCR validation shows AI's effectiveness in identifying biomarkers, enabling prompt treatment to halt disease progression. - Source: PubMed
Publication date: 2026/01/30
Hossein Zadeh RasoulHossein Zadeh RezaHajimoradi MaryamIslampanah MuhammadZarimeidani FatemehRahmati RahemAhmadinia MahdiBahrami NaghmehMohamadnia AbdolrezaShafaghi ShadiNazari Elham - This study examined the absorption, distribution, metabolism, and excretion of branaplam in healthy adult male volunteers and, additionally, compared the adult metabolite profiles obtained in plasma and urine to those obtained in infants with type 1 spinal muscular atrophy. Six volunteers received a single oral dose of 140 mg C-branaplam. Blood, plasma, urine, and fecal samples were analyzed using liquid scintillation counting, accelerator mass spectrometry, and liquid chromatography coupled with high-resolution or tandem mass spectrometry to assess radioactivity, generate metabolite profiles, and structurally characterize branaplam metabolites. Pediatric samples from various age groups were also evaluated. Mechanistic in vitro experiments enabled direct comparison between adult and pediatric results. The C-branaplam dose was well tolerated. Pharmacokinetic analysis showed that branaplam and metabolite UFB112 were the main circulating species, exhibiting delayed T (10 and 28 hours, respectively) and prolonged half-lives (218 and 199 hours, respectively). UFB112 formation was exclusively catalyzed by CYP3A4, and its plasma levels increased with age, reflecting hepatic enzyme maturation. Branaplam was primarily eliminated through metabolism. Renally excreted metabolites were formed via oxygenation, glucuronidation, glucosidation, or ribose conjugation, whereas metabolites in feces included glucosidation and oxidative products. Mass balance was almost complete, with 86.6% of the administered radioactivity recovered in urine and feces over 47 days. These findings highlight the pharmacokinetic behavior of branaplam and UFB112, including the role of the 2,2,6,6,-tetramethylpiperidine-1-oxyl moiety, in how metabolism of branaplam changes during physiological development. Mechanistic insights confirm that CYP enzyme ontogeny significantly influences metabolic profiles. SIGNIFICANCE STATEMENT: This study provides a comprehensive overview of the metabolism of the tetramethyl piperidine moiety, contextualizing enzyme maturation by comparing metabolic fates in infants and adults. It also clearly explains human metabolism of branaplam and summarizes a rare Adenosine Triphosphate pathway observed in these studies. - Source: PubMed
Publication date: 2025/12/13
Lozac'h FDemailly ARaccuglia MJames A DWalles MBorowsky BFaller T - To investigate transcriptomic differences in mural trophectoderm (TE) cells of euploid human blastocysts on the basis of their ability to remain attached in extended in vitro culture and to identify gene expression profiles associated with competence for implantation. - Source: PubMed
Publication date: 2025/10/13
Ortega-Jaén DavidCapalbo AntonioMartín ÁngelGil JuliaPardiñas María LuisaMora-Martinez CarlosBoluda-Navarro MireiaMercader AmparoJosé de Los Santos María