Ask about this productRelated genes to: CYP4F11 Blocking Peptide
- Gene:
- CYP4F11 NIH gene
- Name:
- cytochrome P450 family 4 subfamily F member 11
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 19p13.12
- Locus Type:
- gene with protein product
- Date approved:
- 2001-05-17
- Date modifiied:
- 2016-10-05
Related products to: CYP4F11 Blocking Peptide
Related articles to: CYP4F11 Blocking Peptide
- Pediatric populations differ from adults in drug elimination capacity. While current scaling methods account for enzyme and transporter maturation, they overlook comorbidities, such as biliary atresia (BA), a liver disease appearing within the first 2-8 weeks of life that can progress to cirrhosis. Such conditions may impair hepatic drug clearance, requiring dose adjustments. Physiologically based pharmacokinetic (PBPK) tools aim to address such cases and have been advocated to fill gaps in clinical data instead of less formalized and evidence-based guesswork. However, the paucity of systems data in rare disease populations has hindered the development of robust PBPK models. This study used global liquid chromatography and tandem mass spectrometry (LC-MS/MS) proteomics to quantify drug-metabolizing enzymes and transporters in diseased neonatal (n = 13) and infant (n = 12) liver samples, revealing significant expression changes in biliary atresia (BA) livers vs. controls (n = 19). Based on cohort means, CYP2A6, CYP2B6, and CYP2E1 levels were 6-17-fold higher in BA livers compared to controls, while CYP4F11 and CYP20A1 were reduced. UGT1A1, UGT2B4, and UGT2B7 showed up to 16-fold higher abundance in neonates with BA. Among transporters, ABCF1 abundance increased dramatically (46-fold), whereas B3AT/SLC4A1, ADT1/SLC25A4, and S27A5/SLC27A5 were decreased. The observed alterations suggest that assuming similar liver function in BA and non-BA patients has implications, with impact varying by drug clearance pathway. While in silico models can explore this, clinical pharmacokinetic studies in BA are essential for verification. To our knowledge, such studies are absent. Our observations underscore the urgent need for dedicated pharmacokinetic studies in BA patients to improve precision dosing. - Source: PubMed
Publication date: 2026/03/04
Al-Majdoub Zubida MHoward MartynAchour BrahimBarber JillAlizai NavedRostami-Hodjegan Amin - Posttranslational modifications of human enzymes play a crucial role in disease development. 4-hydroxynonenal (4-HNE), a lipid peroxidation product, can modify proteins and disrupt their function. Human cytochrome CYP4F11, involved in lipid metabolism and xenobiotic degradation, was previously shown to be inhibited by 4-HNE in a malaria model, where hemozoin-induced 4-HNE formation occurs in monocytes. However, structural changes to CYP4F11 upon 4-HNE modification had not been described. In this study, we investigated these changes using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and Raman spectroscopy. DSC thermograms revealed an increased energetic barrier to unfolding, suggesting structural reorganization. FTIR data, supported by computational analysis, showed a decrease in alpha-helix content (0.2-2.5%) and an increase in beta-structure (2.2-3.3%), along with altered disordered regions. Raman spectroscopy indicated significant changes in luminescence decay across emission wavelengths. These structural alterations induced by 4-HNE conjugation (protein lipoxidation) may significantly influence the enzymatic activity of CYP4F11, with potential implications for lipid metabolism and xenobiotic detoxification. - Source: PubMed
Gnatyuk OlenaSkorokhod OleksiiDamin AlessandroChaika MykhailoNaeimaeirouhani FatemePica LorisTomatis AnitaSmorygo AleksandraVoitsitskyi TarasCatucci GianlucaDovbeshko GalynaGilardi Gianfranco - Lung cancer is the leading cause of cancer deaths worldwide with non-small cell lung cancer (NSCLC) as the predominant subtype. Drug resistance in patients with NSCLC often limits treatment effectiveness, underscoring the need for novel therapeutic targets. We have previously demonstrated that a knockdown of CYP4F11 attenuates the proliferation and migration of NCI-H460 cells. CYP4F11 is a fatty acid ω-hydroxylase and metabolizes arachidonic acid to the important lipid mediator 20-hydroxyeicosatetraenoic acid. However, the underlying mechanism of how CYP4F11 promotes cancer progression is unknown. Here, we first confirmed that a genetic ablation of CYP4F11 reduces cell proliferation and migration in an additional NSCLC cell line. Conversely, CYP4F11 overexpression markedly enhanced proliferation and migration in both cell models, underlining the relevance of CYP4F11 as a putative drug target. To further examine the impact of CYP4F11, transcriptomic profiling was conducted comparing CYP4F11 knockdown and control cells. Most intriguingly, fatty acid desaturase 2 (FADS2), a key enzyme in arachidonic acid biosynthesis, was one of the most significantly downregulated genes. Further validation confirmed a significant downregulation of FADS2 at both mRNA and protein levels in CYP4F11 knockdown cells, while a CYP4F11 overexpression triggered its expression. This suggests a regulatory mechanism between CYP4F11 and FADS2 through the joint metabolite arachidonic acid. Collectively, our studies identify CYP4F11 as a promoter of NSCLC cell proliferation and migration and establish a crosstalk between CYP4F11 and FADS2. This work provides new mechanistic insights into lipid metabolism-driven oncogenesis and highlights CYP4F11 as a promising therapeutic target for NSCLC. SIGNIFICANCE STATEMENT: CYP4F11 promotes non-small cell lung cancer progression by driving cell proliferation and migration, as evidenced by both loss-of-function and gain-of-function assays. Importantly, we for the first time identified a positive association between CYP4F11 and fatty acid desaturase 2, uncovering a previously unrecognized tumorigenic mechanism at the cancer-lipid metabolism interface that provides new opportunities for targeted intervention. - Source: PubMed
Publication date: 2025/12/17
Jia HuitingBrixius-Anderko Simone - The cytochrome P450 enzyme CYP4F11, a pivotal regulator of fatty acid metabolism and drug metabolism, exhibits significantly overexpression in non-small cell lung cancer (NSCLC) and is associated with poor clinical outcomes. Through integrated analysis of TCGA/GEO datasets and immunohistochemistry validation of 235 NSCLC specimens, we established CYP4F11 as a novel prognostic biomarker. Functional studies demonstrated that CYP4F11 knockdown markedly impaired NSCLC cell proliferation, clonogenicity, and migration in vitro, moreover xenograft models confirmed its tumor-promoting role in vivo. Mechanistically, we identified CYP4F11 as a direct target of tumor suppressor miR-195 via 3'-UTR binding, with miR-195-mediated suppression of CYP4F11 leading to ubiquitin-proteasomal degradation of mitochondrial malic enzyme 2 (ME2) - a critical metabolic regulator in cancer cells. Metabolomic analyses revealed that CYP4F11 depletion disrupts mitochondrial malate metabolism, while rescue experiments confirmed ME2's pivotal role in mediating CYP4F11's oncogenic effects. Our findings elucidate the CYP4F11/miR-195/ME2 regulatory axis as a crucial determinant of NSCLC progression, highlighting CYP4F11 as both a prognostic indicator and a potential therapeutic target through modulation of cancer cell metabolism. - Source: PubMed
Publication date: 2025/12/08
Shi ShanZhou JiaoLuo QiuyunChen HongtaoYang JingYang LiqiongZhang LinZhang HongyuYang Dajun - Cytochrome P450 enzymes (CYP, P450) are indispensable for human health and catalyse a plethora of reactions contributing to the clearance of xenobiotics, steroid and bile acid biosynthesis, and the functionalization of vitamins in the human body. The family of CYP4F fatty acid ω-hydroxylases consists of five isoforms, CYP4F2, CYP4F3A, CYP4F3B, CYP4F11 and CYP4F22, which share a high amino acid sequence similarity but assume different physiological functions in humans. While CYP4F2 and CYP4F3B are the major enzymes producing a lipid mediator from arachidonic acid, CYP4F3A inactivates leukotriene B4 as anti-inflammatory response, CYP4F11 is capable of effectively metabolizing drugs, and CYP4F22 contributes to a healthy skin barrier. In this review, we provide an overview of recent developments in CYP4F function and discuss potential future directions underlining their growing relevance in human health and disease. - Source: PubMed
Publication date: 2025/08/27
Alves Chagas Brisa CarolineJia HuitingBrixius BjoernBrixius-Anderko Simone