CYP2A6

Last update 08 May 2025

Basic Info

Synonyms

1,4-cineole 2-exo-monooxygenase, Coumarin 7-hydroxylase, CPA6

+ [10]

Introduction

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.

100 Clinical Results associated with CYP2A6

100 Translational Medicine associated with CYP2A6

0 Patents (Medical) associated with CYP2A6

1,737

Literatures (Medical) associated with CYP2A6

01 Jun 2025·Toxicology Reports

Ameliorative role of naringenin in MPTP- induced Parkinsonism: Insights from Drosophila melanogaster experimental model combined with computational biology

Article

Author: Abolaji, Amos Olalekan ; Okonta, Clive ; Ogunyemi, Oludare Michael ; Olabuntu, Babatunde

This study probed the ameliorative effects of naringenin in a D. melanogaster model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, incorporating computational analysis. Initially, flies were treated with naringenin (100-500 µM) and MPTP (250-750 µM) for 14 days in two separate studies to determine the optimum concentrations for the treatments. Following this, optimum naringenin concentrations (100 and 300 µM) were administered to MPTP (500 µM)-exposed flies in a 4-day study. Motor function, survival rate, and neurotoxicity biomarkers were assessed alongside biological network analysis and molecular docking simulation. Results indicate that naringenin exhibits hormetic behavior, with 100-300 µM providing optimal neuroprotection. The treatments significantly improved negative geotaxis and acetylcholinesterase activity, and reduced MPTP-induced oxidative stress as indicated by reduced nitric oxide, hydrogen peroxide, and protein carbonyl levels. Furthermore, naringenin restored thiol contents, and enhanced catalase and glutathione-S-transferase activities. Network analysis helped to identify key targets, including DRD4, DRD2, NFKB1, MAOB, MAPK14, and CYP2A6, which function in dopaminergic signaling and oxido-inflammatory pathways. Molecular docking analysis revealed strong binding interactions of naringenin with DRD2, MAO, MAPK, and NF-κB protein targets, primarily through hydrogen bonding and hydrophobic interactions. Overall, these findings suggest that naringenin mitigates MPTP-induced neurotoxicity by enhancing dopaminergic neurotransmission and suppressing oxidative stress and inflammation. This study further supports the neuroprotective potential of naringenin and could be suggested as a promising nutraceutical/drug candidate for Parkinson's disease.

01 Jun 2025·Gene

Pharmacogenomic variants in the Pumi population from Yunnan, China

Article

Author: Zhang, Xinyu ; Wang, Ying ; Zhang, Chan ; Cheng, Yujing ; Yang, Xin ; Li, Qi ; Chen, Wanlu

BACKGROUNDPharmacogenomics is used to identify genetic factors that influence drug responses, thereby optimizing therapeutic outcomes and reducing adverse effects. The objective of this study is to identify pharmacogenomic variations and their clinical relevance to drug metabolism and toxicity within the Pumi population.METHODSEighty-two genetic variants in 43 genes were genotyped in 200 unrelated Pumi individuals using the Agena MassARRAY Assay. Chi-square tests, adjusted for multiple comparisons with Bonferroni correction, were used to compare genotype frequency divergences between the Pumi population and 26 other populations. Population genetic structure diversity and pairwise F-statistics (Fst) were assessed across 27 populations using Structure v2.3.1 and Arlequin v3.5 software.RESULTSAfter Bonferroni correction, a number of single nucleotide variations (SNVs) exhibited significant differences in frequency between the Pumi population and other populations. The allele frequencies of ADH1A rs975833, ADH1B rs1229984, TPMT rs1142345, and CYP2A6 rs8192726 in the Pumi population were notably different from the East Asian population or the other 26 populations. PharmGKB data indicate that rs1229984, rs1142345, and rs8192726 are associated with the metabolic efficiency of acetaldehyde, mercaptopurine, and efavirenz, respectively. Additionally, the genetic structure analysis (K = 5) and pairwise Fst calculations revealed that the Pumi population shared a similar genetic background with CHB (Fst = 0.031), JPT (Fst = 0.033), KHV (Fst = 0.035), CHS (Fst = 0.036), and CDX (Fst = 0.037) populations.CONCLUSIONOur findings reveal unique genetic variations and biomarkers within the Pumi population, which contributes pharmacogenomic insights and theoretical foundations for personalized medicine tailored to the Pumi population.

03 Apr 2025·Carcinogenesis

Smoking behavior-related genetic variants and lung cancer risk in Japanese: an assessment by mediation analysis

Article

Author: Yamamoto, Sayaka ; Tanoue, Shiroh ; Koyanagi, Yuriko N ; Kubo, Yoko ; Ishizu, Masashi ; Iwashita, Yuji ; Fujiwara, Yutaka ; Ikezaki, Hiroaki ; Kato, Yasufumi ; Takashima, Naoyuki ; Koriyama, Chihaya ; Shinozaki, Tomohiro ; Otonari, Jun ; Kasugai, Yumiko ; Niimi, Akio ; Nakatochi, Masahiro ; Momozawa, Yukihide ; Watanabe, Takeshi ; Koyama, Teruhide ; Suzuki, Sadao ; Nakamura, Yohko ; Nagayoshi, Mako ; Matsuo, Keitaro ; Nakagawa-Senda, Hiroko ; Tomida, Satomi ; Oze, Isao ; Ito, Hidemi ; Hara, Megumi ; Wakai, Kenji ; Michihata, Nobuaki ; Tamura, Takashi ; Sakakura, Noriaki ; Nishida, Yuichiro ; Kadota, Aya

AbstractCigarette smoking is one of the most important risk factors for lung cancer. Genetic studies have shown that smoking behavior-related genetic variants are directly associated with lung cancer, independent of smoking behavior, mainly in European populations. A recent genome-wide association study in Japan identified five loci associated with the number of cigarettes smoked per day. This study aimed to evaluate whether these loci are associated with lung cancer risk directly or indirectly through changing smoking behavior. Here, we conducted a case-control study (1427 cases and 5595 controls) and a prospective cohort study (128 incident cases in 10 520 subjects). Using mediation analysis, we decomposed the total effect of the lead single nucleotide polymorphism (SNP) at each locus on lung cancer risk into direct and indirect effects. The results of the two studies were pooled using a random-effects model to estimate summary relative risks (RRs) and their 95% confidence intervals (CIs). Two studies showed that: (i) rs78277894 (EPHX2-CLU, G > A) had a protective direct effect (RR: 0.84; 95% CI: 0.77–0.93) on lung cancer risk; and (ii) rs56129017 (CYP2A6, C > T) had carcinogenic direct and indirect effects on lung cancer risk (RR: 1.26; 95% CI: 1.15–1.39 and RR: 1.01; 95% CI: 1.00–1.01, respectively). This mediation analysis revealed that two smoking behavior-related SNPs, EPHX2-CLU rs78277894 and CYP2A6 rs56129017, were associated with lung cancer risk through pathways independent of changing smoking behavior. Our findings may contribute to our understanding of lung carcinogenesis pathways that cannot be addressed by changes in smoking behavior.

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CYP2A6

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