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Last update 08 May 2025

CYP4Z1

Last update 08 May 2025

Basic Info

Synonyms

CYP4A20, CYP4Z1, CYPIVZ1

+ [4]

Introduction

A cytochrome P450 monooxygenase that catalyzes the in-chain oxidation of fatty acids (PubMed:19090726, PubMed:29018033). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates lauric and myristic acids predominantly at the omega-4 and omega-2 positions, respectively (PubMed:19090726, PubMed:29018033). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA). Displays an absolute stereoselectivity in the epoxidation of arachidonic acid producing the 14(S),15(R)-epoxyeicosatrienoic acid (EET) enantiomer (PubMed:29018033). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:19090726, PubMed:29018033).

Drugs associated with CYP4Z1

Compound 7c (China Pharmaceutical University)

Target

CYP4Z1

Mechanism

CYP4Z1 modulators

Active Org.

Shandong University

Originator Org.

China Pharmaceutical University

Active Indication

HIV Infections

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

HET-0016

Target

CYP4Z1

Mechanism

CYP4Z1 antagonists

Active Org.

China Pharmaceutical University

Originator Org.

China Pharmaceutical University

Active Indication

Breast Cancer

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CYP4Z1

100 Translational Medicine associated with CYP4Z1

0 Patents (Medical) associated with CYP4Z1

Literatures (Medical) associated with CYP4Z1

01 Jun 2024·Drug Metabolism and Disposition

There and Back Again: A Perspective on 20 Years of CYP4Z1

Review

Author: Kowalski, John P. ; Kowalski, John P ; Rettie, Allan E ; Rettie, Allan E.

Cytochrome P450 (CYP)4Z1, a highly expressed CYP gene in breast cancer, was one of the last CYPs to be identified in the human genome, some 20 years ago. CYP4 enzymes typically catalyze ω-hydroxylation and metabolize ω3 and ω6 polyunsaturated fatty acids to bioactive lipid metabolites that can influence tumor growth and metastasis. These attributes of CYP4Z1 make it an attractive target for new chemotherapeutic drug design, as a potential biomarker for selection of patients that might respond favorably to drugs and for developing enzyme inhibitors as potential therapeutic agents. This review summarizes the current state of knowledge regarding the advancing biochemistry of CYP4Z1, its role in breast cancer, and the recent synthesis of selective chemical inhibitors of the enzyme. We identify gaps that need to be filled to further advance this field and present new experimental data on recombinant CYP4Z1 expression and purification of the active catalytic form. SIGNIFICANCE STATEMENT: In breast cancer, an unmet need is the availability of highly effective therapeutic agents, especially for triple negative breast cancer. The relevance of the work summarized in this mini-review is that it identifies a new potential drug target, CYP4Z1, and discusses ways in which the gene product's catalytic activity might be modulated in order to combat this malignancy and limit its spread.

01 Mar 2024·Environmental Toxicology

1‐Benzylimidazole attenuates the stemness of breast cancer cells through partially targeting CYP4Z1

Article

Author: Liu, Hai ; Yuan, Yaqin ; Guo, Qianqian ; Zhou, Yi ; Yuan, Manqin ; Zhang, Yujie ; Qin, Hai ; Xi, Tao

AbstractCytochrome P450 (CYP) 4Z1 (CYP4Z1) has recently garnered much interest as its expression predicts a poor prognosis and as a oncogene in breast cancer, and overexpressed in other many cancers. We previously showed that CYP4Z1 acts as a promoter of cancer stem cells (CSCs) to facilitate the occurrence and development of breast cancer. Here, RNA sequencing found that 1‐benzylimidazole (1‐Benzy) held a preferable correlation with breast cancer and suppressed the expression of CSC makers. Further functional experiments, including mammary spheroid formation, wound‐healing, transwell‐invasion, detection of tumor initiation, and metastatic ability, showed that 1‐Benzy suppressed the stemness and metastasis of breast cancer cells. Additionally, we further demonstrated that CYP4Z1 is necessary for 1‐Benzy‐mediated suppression on breast cancer stemness and 1‐Benzy exerted a weaker effect in breast cancer cells with CYP4Z1 knockdown. Taken together, our data suggest that 1‐Benzy might be a potential drug suppressing breast cancer stemness via targeting CYP4Z1.

01 Jan 2023·Cancer Reports

Quantification of spatial pharmacogene expression heterogeneity in breast tumors

Article

Author: Silvola, Rebecca M. ; Skaar, Todd C. ; Powell, Nicholas R. ; Howard, John S. ; Ipe, Joseph ; Badve, Sunil

AbstractBackgroundChemotherapeutic drug concentrations vary across different regions of tumors and this is thought to be involved in development of chemotherapy resistance. Insufficient drug delivery to some regions of the tumor may be due to spatial differences in expression of genes involved in the disposition, transport, and detoxification of drugs (pharmacogenes). Therefore, in this study, we analyzed the spatial expression of 286 pharmacogenes in six breast cancer tissues using the recently developed Visium spatial transcriptomics platform to (1) determine if these pharmacogenes are expressed heterogeneously across tumor tissue and (2) to determine which pharmacogenes have the most spatial expression heterogeneity.Methods and ResultsThe spatial transcriptomics technology sequences the transcriptome of 55 um diameter barcoded sections (spots) across a tissue sample. We analyzed spatial gene expression profiles of four biobank‐sourced breast tumor samples in addition to two breast tumor sample datasets from 10× Genomics. We define heterogeneity as the interquartile range of read counts. Collectively, we identified 8887 spots in tumor regions, 3814 in stroma, 44 in lymphocytes, and 116 in normal regions based on pathologist annotation of the tissues. We showed statistically significant differences in expression of pharmacogenes in tumor regions compared to surrounding non‐tumor regions. We also observed that the most heterogeneously expressed genes within tumor regions were involved in reactive oxygen species (ROS) handling and detoxification mechanisms. GPX4, GSTP1, MGST3, SOD1, CYP4Z1, CYB5R3, GSTK1, and NAT1 showed the most heterogeneous expression within tumor regions.ConclusionsThe heterogeneous expression of these pharmacogenes may have important implications for cancer therapy due to their ability to impact drug distribution and efficacy throughout the tumor. Our results suggest that chemoresistance caused by expression of GPX4, GSTP1, MGST3, and SOD1 may be intrinsic, not acquired, since the heterogeneity is not specific to chemotherapy‐treated samples or cell type. Additionally, we identified candidate chemoresistance pharmacogenes that can be further tested through focused follow‐up studies.

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CYP4Z1

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