SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions

Preissner, Saskia; Kroll, Katharina; Dunkel, Mathias; Senger, Christian; Goldsobel, Gady; Kuzman, Daniel; Guenther, Stefan; Winnenburg, Rainer; Schroeder, Michael; Preißner, Robert

doi:10.1093/nar/gkp970

Cited by 217 publications

(135 citation statements)

References 29 publications

(32 reference statements)

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…Pharmacokinetic and drug-drug interaction (DDI) studies involving DOAs were obtained from the literature (see Appendix). Four databases were used to identify the status (substrate, inhibitor and/or inducer) of each molecule involved in DOA transport (Pgp) or hepatic metabolism (CYP3A4), namely SuperCYP [27], Drug Bank [28], Gene Cards [29], and the summary of product characteristics. Drug inhibitor and inducer effect on Pgp and CYP3A4 were then merged into a common database.…”

Section: Methodsmentioning

confidence: 99%

Risk of Direct Oral Anticoagulant Bioaccumulation in Patients with Pulmonary Hypertension

Gabriël¹,

Delavenne²,

Bedouch³

et al. 2016

Respiration

View full text Add to dashboard Cite

Background: Patients treated for pulmonary arterial hypertension (PAH) frequently receive vitamin K antagonists (VKAs) for PAH or validated indications (such as atrial fibrillation or venous thromboembolism). In these latter indications, VKAs are challenged by direct oral anticoagulants (DOAs). Decreased dosage of DOAs has been proposed in patients at risk of bioaccumulation. Objectives: We aimed to evaluate the frequency of bioaccumulation risks in patients treated with PAH-targeted therapy, particularly regarding the presence of validated indications. Methods: We conducted a retrospective study in three different PAH referral centers. All patients receiving PAH-targeted therapy were classified according to demographics, prescription and indications of VKAs, and the presence of major bioaccumulation risk factors (renal failure, low body weight, strong P-glycoprotein or cytochrome P3A4 inhibitors). Results: Two hundred and thirty-nine of the 366 patients included received VKAs, 94 for validated indications. At least one major risk factor was found in 231 (63.1%) of the whole study population, and in 54 (57.4%) of the patients anticoagulated for a validated indication. No specific patient phenotype could be individualized. Conclusions: About 1 in 2 patients treated with PAH therapy has at least one of the three major risk factors for DOA bioaccumulation. DOAs in the PH setting could be associated with bioaccumulation and should be individualized, mainly in patients with confirmed indication.

show abstract

Section: Methodsmentioning

confidence: 99%

Risk of Direct Oral Anticoagulant Bioaccumulation in Patients with Pulmonary Hypertension

Gabriël¹,

Delavenne²,

Bedouch³

et al. 2016

Respiration

View full text Add to dashboard Cite

show abstract

“…On the contrary, if the nsSNPs can abolish or reduce enzymatic activity of CYP, the drugs metabolized by such CYP cannot be metabolized safely and the associated side effects may occur. Although there are some database for the effects of nsSNPs on CYPs activity [33,53], estimating such effects of nsSNPs is also important for investigating drug responses among different patients and predicting clinical implication of the novel genetic variants in CYP genes. …”

Section: Snp and Drug Metabolismmentioning

confidence: 99%

Recent Progress on Structural Bioinformatics Research of Cytochrome P450 and Its Impact on Drug Discovery

Zhang

Wei

2014

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Cytochrome P450 is predominantly responsible for human drug metabolism, which is of critical importance for drug discovery and development. Structural bioinformatics focuses on analysis and prediction of three-dimentional structure of biological macromolecules and elucidation of structure-function relationship as well as identification of important binding interactions. Rapid advancement of structural bioinformatics has been made over the last decade. With more information available for CYP structures, the methods of structural bioinformatics may be used in the CYP field. In this review, we demonstrate three previous studies on CYP using the methods of structural bioinformatics, including the investigation of reasons for decrease of enzymatic activity of CYP1A2 caused by a peripheral mutation, the construction of a pharmacophore model specific to active site of CYP1A2 and the prediction of the functional consequences of single residue mutation in CYP. By illustrating these studies we attempt to show the potential role of structural bioinformatics in CYP research and help better understanding the importance of structural bioinformatics in drug designing.

show abstract

“…TH behaves similarly to a steroid hormone, and most steroid hormones are substrates for the CYP3A4 enzyme isoform [43]. There is strong evidence that when the CYP3A4 isoform is induced, TH glucuronidation and sulfation are also induced [20,[43][44][45]. Notably, many drugs that relieve or worsen WED symptoms are inducers or inhibitors, respectively, of the CYP3A4 isoform (Table 1).…”

Section: Drug-induced Willis-ekbom Diseasementioning

confidence: 99%

Willis-Ekbomdisease (Restless Legs Syndrome) Pathophysiology: The Imbalance Between Dopamine and Thyroid Hormone Theory

Pereira¹,

Pradella-Hallinan²

2013

J Sleep Disorders Ther

View full text Add to dashboard Cite

Willis-Ekbom disease (WED), also known as restless legs syndrome, is generally accepted as a disease of unknown pathophysiology, though it is believed that dysfunctions in the dopaminergic system and iron metabolism may play a role. However, an increasing body of evidence points to the insufficient modulation of thyrotropin hormone by the neurohormone dopamine (DA) as the underlying mechanism of the disease pathology. Additionally, it has generally been accepted that the annoying symptoms of the disease are generated inside the Blood Brain Barrier (BBB). This assumption, which has little evidence supporting it, has been weakened by the recent observation that domperidone, a DA blocking agent that does not cross the BBB, worsens the severity of WED symptoms. In 1974, it was discovered that levodopa dramatically relieves WED symptoms, thus supporting the hypothesis that insufficient dopaminergic function contributes to WED pathogenesis. Earlier, in 1970, it was observed that venous infusion of DA diminishes thyrotropin levels, and from clinical studies, it is known that WED symptoms are worse in the evening and night, when thyrotropin activity increases. Furthermore, drugs that alleviate WED symptoms increase the DA activity or decrease the Thyroid Hormone (TH) activity, whereas drugs that worsen WED tend to have the opposite effects on DA and TH activity. In this article, we present robust evidence to support the hypothesis that WED is caused by an imbalance between DA and TH and that its symptoms are generated in the periphery of the somatosensory system. We theorize that WED should be considered a functional peripheral neuropathy.

show abstract

SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions

Cited by 217 publications

References 29 publications

Risk of Direct Oral Anticoagulant Bioaccumulation in Patients with Pulmonary Hypertension

Risk of Direct Oral Anticoagulant Bioaccumulation in Patients with Pulmonary Hypertension

Recent Progress on Structural Bioinformatics Research of Cytochrome P450 and Its Impact on Drug Discovery

Willis-Ekbomdisease (Restless Legs Syndrome) Pathophysiology: The Imbalance Between Dopamine and Thyroid Hormone Theory

Contact Info

Product

Resources

About