CYP2J2 Molecular Recognition: A New Axis for Therapeutic Design

Das, Aditi; Weigle, Austin T.; Arnold, William R.; Kim, Justin S.; Carnevale, Lauren N.; Huff, Hannah C.

doi:10.1016/j.pharmthera.2020.107601

Cited by 37 publications

(25 citation statements)

References 337 publications

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“…They measured IC50 values of already known 11 CYP2D 6 ligands by using 7-methoxy-4-(aminomethyl) coumarin (MAMC) as substrate [ 57 ]. The crystallized rabbit CYP2 C5 based homology model was generated, and its capacity to reproduce binding sequences related to the substrates' metabolic orientation was maintained during direct molecular dynamics simulations [ 58 ]. The electrostatic potential of CYP2D and CYP2D 1-4 actives binding sites showed affinities towards ligands.…”

Section: Discussionmentioning

confidence: 99%

[Retracted] In Silico Structural, Functional, and Phylogenetic Analysis of Cytochrome (CYPD) Protein Family

Ahmad

Afzal

Jamal

et al. 2021

BioMed Research International

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Cytochrome (CYP) enzymes catalyze the metabolic reactions of endogenous and exogenous compounds. The superfamily of enzymes is found across many organisms, regardless of type, except for plants. Information was gathered about CYP2D enzymes through protein sequences of humans and other organisms. The secondary structure was predicted using the SOPMA. The structural and functional study of human CYP2D was conducted using ProtParam, SOPMA, Predotar 1.03, SignalP, TMHMM 2.0, and ExPASy. Most animals shared five central motifs according to motif analysis results. The tertiary structure of human CYP2D, as well as other animal species, was predicted by Phyre2. Human CYP2D proteins are heavily conserved across organisms, according to the findings. This indicates that they are descended from a single ancestor. They calculate the ratio of alpha-helices to extended strands to beta sheets to random coils. Most of the enzymes are alpha-helix, but small amounts of the random coil were also found. The data were obtained to provide us with a better understanding of mammalian proteins’ functions and evolutionary relationships.

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Section: Discussionmentioning

confidence: 99%

[Retracted] In Silico Structural, Functional, and Phylogenetic Analysis of Cytochrome (CYPD) Protein Family

Ahmad

Afzal

Jamal

et al. 2021

BioMed Research International

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“…This system is approached by U.S. Food and Drug Administration to treat several diseases ( Gruntman and Flotte, 2018 ). On the other hand, with the development of computer technique, the molecular secret of CYP 2J2 could be deeply discovered and potential drugs enhancing their activities might be a potential strategy for therapeutic design ( Das et al, 2020 ).…”

Section: Drug Development-related Eets Against Cardiac Remodelingmentioning

confidence: 99%

The Role of Epoxyeicosatrienoic Acids in Cardiac Remodeling

Lai

Chen

2021

Front. Physiol.

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Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by cytochrome P450 (CYP) epoxygenases, which include four regioisomers: 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET. Each of them possesses beneficial effects against inflammation, fibrosis, and apoptosis, which could combat cardiovascular diseases. Numerous studies have demonstrated that elevation of EETs by overexpression of CYP2J2, inhibition of sEH, or treatment with EET analogs showed protective effects in various cardiovascular diseases, including hypertension, myocardial infarction, and heart failure. As is known to all, cardiac remodeling is the major pathogenesis of cardiovascular diseases. This review will begin with the introduction of EETs and their protective effects in cardiovascular diseases. In the following, the roles of EETs in cardiac remodeling, with a particular emphasis on myocardial hypertrophy, apoptosis, fibrosis, inflammation, and angiogenesis, will be summarized. Finally, it is suggested that upregulation of EETs is a potential therapeutic strategy for cardiovascular diseases. The EET-related drug development against cardiac remodeling is also discussed, including the overexpression of CYP2J2, inhibition of sEH, and the analogs of EET.

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“…Furthermore, some studies suggest that CYP variants mediating weaker AA metabolism can contribute to kidney damage ( 59 ) and that carriers of loss-of-function alleles CYP2C9 *2 and CYP2C9 *3 have reduced EET production ( 60 ). Furthermore, loss-of-function CYP2C8 *3, CYP2C9 *2, CYP2C9 *3, and CYP2J2 *7 variants have been associated with endothelial dysfunction, myocardial infarction, and stroke ( 61 , 62 , 63 , 64 ).…”

Section: Discussion and Review Of Drug-drug-gene Interactionsmentioning

confidence: 99%

Drug-drug-gene interactions as mediators of adverse drug reactions to diclofenac and statins: a case report and literature review

Božina

Ganoci

Šimičević

et al. 2021

Archives of Industrial Hygiene and Toxicology

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Concomitant treatment with drugs that inhibit drug metabolising enzymes and/or transporters, such as commonly prescribed statins and nonsteroidal anti-inflammatory drugs (NSAIDs), has been associated with prolonged drug exposure and increased risk of adverse drug reactions (ADRs) due to drug-drug interactions. The risk is further increased in patients with chronic diseases/comorbidities who are more susceptible because of their genetic setup or external factors. In that light, we present a case of a 46-year-old woman who had been experiencing acute renal and hepatic injury and myalgia over two years of concomitant treatment with diclofenac, atorvastatin, simvastatin/fenofibrate, and several other drugs, including pantoprazole and furosemide. Our pharmacogenomic findings supported the suspicion that ADRs, most notably the multi-organ toxicity experienced by our patient, may be owed to drug-drug-gene interactions and increased bioavailability of the prescribed drugs due to slower detoxification capacity and decreased hepatic and renal elimination. We also discuss the importance of CYP polymorphisms in the biotransformation of endogenous substrates such as arachidonic acid and their modulating role in pathophysiological processes. Yet even though the risks of ADRs related to the above mentioned drugs are substantially evidenced in literature, pre-emptive pharmacogenetic analysis has not yet found its way into common clinical practice.

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CYP2J2 Molecular Recognition: A New Axis for Therapeutic Design

Cited by 37 publications

References 337 publications

[Retracted] In Silico Structural, Functional, and Phylogenetic Analysis of Cytochrome (CYPD) Protein Family

[Retracted] In Silico Structural, Functional, and Phylogenetic Analysis of Cytochrome (CYPD) Protein Family

The Role of Epoxyeicosatrienoic Acids in Cardiac Remodeling

Drug-drug-gene interactions as mediators of adverse drug reactions to diclofenac and statins: a case report and literature review

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