Ask about this productRelated genes to: CYP1A2 antibody
- Gene:
- CYP1A2 NIH gene
- Name:
- cytochrome P450 family 1 subfamily A member 2
- Previous symbol:
- -
- Synonyms:
- P3-450, CP12
- Chromosome:
- 15q24.1
- Locus Type:
- gene with protein product
- Date approved:
- 1990-04-25
- Date modifiied:
- 2019-04-23
Related products to: CYP1A2 antibody
Related articles to: CYP1A2 antibody
- Cytochrome P450 1A2 (CYP1A2) exhibits substantial interindividual variability, necessitating appropriate phenotyping strategies for personalized pharmacotherapy. This study evaluated endogenous melatonin partial metabolic clearance (CL), calculated from urinary 6-hydroxymelatonin (6-O-MEL) excretion and plasma melatonin (MEL) exposure, as a potential endogenous marker of CYP1A2 activity and compared it with caffeine (CA)-based indexes. - Source: PubMed
Publication date: 2026/04/30
Yokokawa AkitomoShimazaki HayatoIgarashi ShunjiTagawa YoshikiHisada NaokiShibasaki Hiromi - The flavonoid cirsimaritin has pharmacological activities that potentially in modulate inflammatory responses, tumor progression, and glucolipid metabolism. However, its influence on cytochrome P450 (P450) enzyme activity remains unexplored. - Source: PubMed
Publication date: 2026/04/28
Li XiangchengShi YaweiLiu Dandan - PM-4321 is a selective aryl hydrocarbon receptor (AhR) modulator profiled as part of an AhR antagonist program for cancer immunotherapy. The AhR regulates transcription of xenobiotic metabolizing enzymes, including cytochrome P450 (CYP) 1A1 and CYP1A2. Although initial pharmacokinetic studies in preclinical species demonstrated low systemic clearance and high oral bioavailability, repeat-dose pharmacokinetic studies revealed dose- and time-dependent reductions in systemic exposure indicative of metabolic autoinduction. This study sought to elucidate the mechanistic basis of this phenomenon. Despite high metabolic stability in hepatocytes and single dose pharmacokinetic studies, PM-4321 exhibited a decline in systemic exposure after repeat-dosing in mice and monkeys. This was accompanied by robust induction of CYP1A1 and CYP1A2, confirmed by both quantitative polymerase chain reaction and liver transcriptomic profiling. Conventional enzyme phenotyping failed to detect involvement of these enzymes due to low parent compound turnover. However, identification of M457-1, a CYP1A1-specific mono-oxidation metabolite, provided direct evidence of enzyme activity and enabled quantification of the induction response. These findings demonstrate that PM-4321 undergoes AhR-mediated autoinduction via selective upregulation of CYP1A1, a mechanism not readily captured by standard drug metabolism and pharmacokinetics assays. Integration of transcriptomic analysis and metabolite-centric phenotyping was essential to uncover this noncanonical pathway. This work underscores the importance of applying advanced molecular and analytical tools to characterize the disposition of low clearance compounds, particularly those targeting ligand-activated transcription factors such as AhR. SIGNIFICANCE STATEMENT: This study identifies cytochrome P450 1A1 induction as the mechanistic driver of PM-4321 autoinduction and the reduced systemic exposure in preclinical species. By integrating transcriptomic profiling with metabolite-centric phenotyping, we resolved a liability that standard drug metabolism and pharmacokinetics assays failed to capture. This framework offers a practical path for characterizing low-clearance compounds that engage ligand-activated transcription factors, with direct implications for translational pharmacokinetics and drug-drug interaction risk assessment. - Source: PubMed
Publication date: 2026/03/28
Kumar SeemaGoodman KeithYi SueEl-Kattan Ayman FSalter-Cid LuisaRanganath SheilaRamani KritikaDworakowski Wojciech - Gastrointestinal stromal tumors (GIST) can become malignant upon recurrence and metastasis, yet no drugs specifically target these processes. This study explores the effectiveness and mechanism of paeoniflorin in treating GIST. Initially, the impact of paeoniflorin on the viability, proliferation, and migration of GIST cell lines (GIST-T1 and GIST-882) was assessed using CCK-8, transwell, and wound healing assays at low (5 μM) and high (20 μM) concentrations. Subsequently, datasets GSE136755 and GSE21315 were analyzed to identify potential therapeutic targets for inhibiting GIST transfer. Key genes and pathways related to Paeoniflorin's anti-GIST effects were identified through molecular docking and Western blotting. Paeoniflorin influenced cell viability, proliferation, and migration in GIST-T1 and GIST-882 cell lines at low (5 μM) and high (20 μM) concentrations. We identified 761 differentially expressed genes (DEGs) and selected 50 hub genes using a PPI network. By screening paeoniflorin's potential targets, we identified eight key genes (CYP1A2, CYP2C9, CYP3A4, F2, ICAM1, NR1H4, PLG, and SERPINE1) that were significantly elevated in metastatic GIST samples. CYP3A4 was confirmed as a target of Paeoniflorin in GIST treatment through molecular docking and Western blotting. Pan-cancer analysis showed CYP3A4's enrichment in the tight junction pathway and a significant negative correlation with AKT2 protein. Paeoniflorin treatment led to high AKT2 expression in the tight junction pathway in GIST cell lines. Paeoniflorin acts on the CYP3A4 protein to affect the tight junction pathway, inhibiting the malignant metastasis of GIST. - Source: PubMed
Publication date: 2026/04/23
Cui DapengCui ZeyinLi YansenFan ShuangLi LeiYang ChengYu RuixiaCui JiaxinFu RunjiaFei Jiandong - The application of human hepatic cell lines to early drug discovery and development instead of human primary hepatocytes (HPHs) has been limited because of the low level of drug-metabolizing enzymes (DMEs). - Source: PubMed
Yu HanaLee Song HeeKim Ji HyeonKim Seung JinKang Hee Eun