Alternative splicing (AS) is an important molecular mechanism by which single genes can generate multiple mRNA isoforms. We reported previously that, in Oryza sativa, the cyclophilin 19-4 (OsCYP19-4.1) transcript was significantly upregulated in resp...
Estrogens play critical roles in embryonic development, gonadal sex differentiation, behavior, and reproduction in vertebrates and in several human cancers. Estrogens are synthesized from testosterone and androstenedione by the endoplasmic reticulum...
Carbamazepine (CBZ), a commonly prescribed antiepileptic drug, in human liver, is mainly metabolized by two isoforms of cytochrome P450 (CYP), CYP3A4 and CYP3A5. Therefore, the binding of CBZ with these two enzymes plays crucial role in the biotransf...
Progress in understanding the mechanisms of the idiosyncratic drug induced liver injury (iDILI) was highlighted in a scientometric investigation on the knowledge mapping of iDILI throughout the world, but uncertainty remained on metabolic risk factor...
The human cytochrome P450 (CYP) 2C9 and 2C19 enzymes are two highly similar isoforms with key roles in drug metabolism. They are anchored to the endoplasmic reticulum membrane by their N-terminal transmembrane helix and interactions of their cytoplas...
CYP 3A4 and CYP 3A5 are two important members of the human cytochrome P450 family. Although their overall structures are similar, the local structures of the active site are different, which directly leads to obvious individual differences in drug me...
Background/Objectives: Metabolic enzymes are crucial for the detoxification of exogenously administered drugs, especially enzymes expressed in the intestine and the liver. Recent advancements in analytical methodologies enable sensitive and specific...
Galeon, a natural cyclic-diarylheptanoid (CDH), which was first isolated from Myrica gale L., is known to have potent cytotoxicity against A549 cell lines, anti-tubercular activity against Mycobacterium tuberculosis H37Rv, chemo-preventive potential,...
Kratom alkaloids are classified as aromatic pentacyclic indole and substituted carbonyl oxindole alkaloids. This study investigates the metabolism and interactions of indole alkaloids using in silico tools, including ADMET Predictor 13.0™, to a...
Human cytochrome P450 enzymes (CYPs) are heme-containing monooxygenases. This superfamily of drug-metabolizing enzymes is responsible for the metabolism of most drugs and other xenobiotics. The inhibition of CYPs may lead to drug–drug interacti...
The activity of microsomal cytochromes P450 (CYP) is strictly dependent on the supply of electrons provided by NADPH cytochrome P450 oxidoreductase (CPR). The variant nature of the isoform-specific proximal interface of microsomal CYPs implies that t...
Human individual differences in brain cytochrome P450 (CYP) metabolism, including induction, inhibition, and genetic variation, may influence brain sensitivity to neurotoxins and thus participate in the onset of neurodegenerative diseases. The aim of...
The human small intestine can be involved in the first-pass metabolism of drugs. Under this condition, members of the CYP450 superfamily are expected to contribute to drug presystemic biotransformation. The aim of this study was to quantify protein e...
The characterization of novel radiotracers toward their metabolic stability is an essential part of their development. While in vitro methods such as liver microsome assays or ex vivo blood or tissue samples provide information on overall stability,...
Background: Cytochrome P450 (CYP450) enzymes play a central role in the metabolism of xenobiotics, including plant-derived compounds such as terpenoids. Objectives: This study aimed to predict the molecular interactions of linalool (LIN) and linalyl...
Bacopa monnieri and the constituents of this plant, especially bacosides, possess various neuropharmacological properties. Like drugs, some herbal extracts and the constituents of their extracts alter cytochrome P450 (CYP) enzymes, causing potential...
20 January 2023
Arsenic (As) is a common contaminant in drinking water in northeastern Mexico, which reduces the expression of cytochrome P450 (CYP 450). This enzyme group metabolizes numerous drugs, such as oral antidiabetic drugs such as pioglitazone (61% CYP 3A4,...
Various diseases such as type 2 diabetes (T2D) may alter drug clearance. The objective of this study was to evaluate the effects of T2D on CYP450 expressions and activities using high-fat diet (HFD) as a model of obesity-dependent diabetes in C57BL6...
Heptachlor (HEP) is an insecticide metabolized by cytochrome P450 (CYP) enzymes in the human liver, resulting in the formation of heptachlor epoxide (HEPX). HEPX can persist in the human body for a long duration. Therefore, it can be extremely harmfu...
In some cases, the formation of reactive species from the metabolism of xenobiotics has been linked to toxicity and therefore it is imperative to detect potential bioactivation for candidate drugs during drug discovery. Reactive species can covalentl...
NADPH-cytochrome P450 reductase (CPR) is the unique redox partner of microsomal cytochrome P450s (CYPs). CPR exists in a conformational equilibrium between open and closed conformations throughout its electron transfer (ET) function. Previously, we h...
CYP3A is an enzyme subfamily in the cytochrome P450 (CYP) superfamily and includes isoforms CYP3A4, CYP3A5, CYP3A7, and CYP3A43. CYP3A enzymes are indiscriminate toward substrates and are unique in that these enzymes metabolize both endogenous compou...
Cytochrome P450 (CYP) isozymes vary their expression depending on the brain area, the cell type, and the presence of drugs. Some isoforms are involved in detoxification and/or toxic activation of xenobiotics in central nervous system. However, their...
Drug–drug interactions (DDIs) can cause drug toxicities, reduced pharmacological effects, and adverse drug reactions. Studies aiming to determine the possible DDIs for an investigational drug are part of the drug discovery and development process and...
Treatment of behavioral and psychological symptoms of dementia (BPSD) and comorbidities often necessitates the concomitant use of antipsychotics and non-antipsychotic drugs, thereby potentiating the risk for drug–drug interactions (DDIs). The p...
Like flavonoids, biflavonoids, dimeric flavonoids, and polyphenolic plant secondary metabolites have antioxidant, antibacterial, antiviral, anti-inflammatory, and anti-cancer properties. However, there is limited data on their effects on cytochrome P...
Background/Objectives: Gold(I) complexes are promising bioactive agents with anticancer and anti-inflammatory potential. This study evaluated cytochrome P450 (CYP) interactions and in vitro pharmacokinetic properties of two Au(I)–triphenylphosp...
Selaginella tamariscina (Beauv.) has been used for traditional herbal medicine for treatment of cancer, hepatitis, and diabetes in the Orient. Numerous bioactive compounds including alkaloids, flavonoids, lignans, and selaginellins have been identifi...
Dimethyl sulfoxide (DMSO) is widely used as a solvent for small hydrophobic drug molecules. However, the safe volume allowing to avoid its embryotoxic effect has been poorly studied. In this study, we documented the effects of dimethyl sulfoxide (DMS...
Tamoxifen remains a cornerstone of treatment for patients with oestrogen-receptor-positive breast cancer. Tamoxifen efficacy depends on the biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoform, to the active metabolite endoxi...
Venetoclax, a BCL-2 inhibitor used to treat certain hematological cancers, exhibits low oral bioavailability and high interpatient pharmacokinetic variability. Venetoclax is commonly administered with prophylactic antifungal drugs that may result in...
Loxoprofen, a propionic acid derivative, non-steroidal anti-inflammatory drug (NSAID) is a prodrug that is reduced to its active metabolite, trans-alcohol form (Trans-OH) by carbonyl reductase enzyme in the liver. Previous studies demonstrated the hy...
Background: Cytochromes P450 (CYPs) are heme-containing oxidoreductase enzymes with mono-oxygenase activity. Human CYPs catalyze the oxidation of a great variety of chemicals, including xenobiotics, steroid hormones, vitamins, bile acids, procarcinog...
Cytochrome P450 (CYP450) is a major drug-metabolizing enzyme system mainly distributed in liver microsomes and involved in the metabolism of many endogenous substances (such as fatty acids and arachidonic acids), and exogenous compounds (such as drug...
Cytochrome P450 3A (CYP3A) enzymes catalyze the metabolism of a wide range of endogenous and exogenous compounds. Genetic variations in the 3 CYP3A isoforms (CYP3A28, CYP3A74, and CYP3A76) may influence their expression and activity, leading to inter...
Human cytochrome P450 enzymes (CYPs) are critical for the metabolism of small-molecule pharmaceuticals (drugs). As such, the prediction of drug metabolism by and drug inhibition of CYP activity is an important component of the drug discovery and desi...
25 December 2015
Glycyrrhetinic acid (GA) has been used clinically in the treatment of patients with chronic hepatitis. This study evaluated the effect of GA on the activity of five P450(CYP450) cytochrome enzymes: CYP2A6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, in huma...
Cinnamomum cassia L. is used as a spice and flavoring agent as well as a traditional medicine worldwide. Diterpenoids, a class of compounds present in C. cassia, have various pharmacological effects, such as anti-inflammatory, antitumor, and ant...
Over the past decade, there have been significant developments in treatment for ovarian cancer, yet the lack of targeted therapy with few side effects still represents a major issue. The cytochrome P450 (CYP) enzyme family plays a vital role in the t...
Despite significant advances in treatment strategies over the past decade, selective treatment of breast cancer with limited side-effects still remains a great challenge. The cytochrome P450 (CYP) family of enzymes contribute to cancer cell prolifera...
Because of the large flexibility and malleability of Cytochrome P450 enzymes (CYPs), in silico prediction of CYP binding affinities to drugs and other xenobiotic compounds is a true challenge. In the current work, we use an iterative linear interacti...
Cytochrome P450 (CYP) enzymes are membrane-bound hemoproteins crucial for drug and xenobiotic metabolism. While more than 50 CYPs have been identified in humans, the isoforms from CYP1, 2, and 3 families contribute to the metabolism of about 80% of c...
Bergamottin (BM, 1), a component of grapefruit juice, acts as an inhibitor of some isoforms of the cytochrome P450 (CYP) enzyme, particularly CYP3A4. Herein, a new bergamottin containing a nitroxide moiety (SL-bergamottin, SL-BM, 10) was synthesized;...
Although significant advances in the treatment of breast cancer have been made over the last few decades, searching for more effective prophylaxis and therapy for this type of cancer is still topical. Orphan cytochromes (CYPs) P450 are enzymes whose...
This study predicted dapaconazole clinical drug–drug interactions (DDIs) over the main Cytochrome P450 (CYP) isoenzymes using static (in vitro to in vivo extrapolation equation, IVIVE) and dynamic (PBPK model) approaches. The in vitro inhibitio...
Background/Objectives: Flavonoids are widely used as lead structures in drug discovery, and their pharmacological and metabolic properties are strongly influenced by structural features such as positional isomerism. This study aimed to compare the me...
A unique cytochrome P450 (CYP) oxidoreductase (CPR) sustains activities of human microsomal CYPs. Its function requires toggling between a closed conformation enabling electron transfers from NADPH to FAD and then FMN cofactors and open conformations...
Seongsanamide A is a bicyclic peptide with an isodityrosine residue discovered in Bacillus safensis KCTC 12796BP which exhibits anti-allergic activity in vitro and in vivo without significant cytotoxicity. The purpose of this study was to elucidate t...
Cytochrome P450 (CYP) enzymes play important roles in metabolising endogenous and xenobiotic substances. Characterisations of human CYP proteins have been advanced with the rapid development of molecular technology that allows heterologous expression...
Polychlorinated dibenzo-p-dioxins (PCDDs) and coplanar polychlorinated biphenyls (PCBs) contribute to dioxin toxicity in humans and wildlife after bioaccumulation through the food chain from the environment. The authors examined human and rat cytochr...
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