Jensen, Ole

[["dc.bibliographiccitation.artnumber","S0006295221003671"],["dc.bibliographiccitation.firstpage","114751"],["dc.bibliographiccitation.journal","Biochemical Pharmacology"],["dc.contributor.author","Sachkova, Alexandra"],["dc.contributor.author","Doetsch, David Alexander"],["dc.contributor.author","Jensen, Ole"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Ansari, Salim"],["dc.date.accessioned","2021-09-01T06:42:42Z"],["dc.date.available","2021-09-01T06:42:42Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1016/j.bcp.2021.114751"],["dc.identifier.pii","S0006295221003671"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89122"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation.issn","0006-2952"],["dc.title","How do psychostimulants enter the human brain? Analysis of the role of the proton-organic cation antiporter"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","12403"],["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","Journal of Medicinal Chemistry"],["dc.bibliographiccitation.lastpage","12416"],["dc.bibliographiccitation.volume","65"],["dc.contributor.author","Gebauer, Lukas"],["dc.contributor.author","Jensen, Ole"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Dücker, Christof"],["dc.date.accessioned","2022-10-04T10:21:11Z"],["dc.date.available","2022-10-04T10:21:11Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1021/acs.jmedchem.2c01075"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114345"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-600"],["dc.relation.eissn","1520-4804"],["dc.relation.issn","0022-2623"],["dc.title","Substrates and Inhibitors of the Organic Cation Transporter 3 and Comparison with OCT1 and OCT2"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","S0006295221004974"],["dc.bibliographiccitation.firstpage","114871"],["dc.bibliographiccitation.journal","Biochemical Pharmacology"],["dc.bibliographiccitation.volume","197"],["dc.contributor.author","Gebauer, Lukas"],["dc.contributor.author","Arul Murugan, N."],["dc.contributor.author","Jensen, Ole"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Rafehi, Muhammad"],["dc.date.accessioned","2022-01-11T14:07:49Z"],["dc.date.available","2022-01-11T14:07:49Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1016/j.bcp.2021.114871"],["dc.identifier.pii","S0006295221004974"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97873"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation.issn","0006-2952"],["dc.title","Molecular basis for stereoselective transport of fenoterol by the organic cation transporters 1 and 2"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","113731"],["dc.bibliographiccitation.journal","Biochemical Pharmacology"],["dc.bibliographiccitation.volume","171"],["dc.contributor.author","Jensen, Ole"],["dc.contributor.author","Rafehi, Muhammad"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.date.accessioned","2020-10-22T08:56:04Z"],["dc.date.available","2020-10-22T08:56:04Z"],["dc.date.issued","2020"],["dc.description.abstract","Stereoselectivity is well described for receptor binding and enzyme catalysis, but so far has only been scarcely investigated in carrier-mediated membrane transport. We thus studied transport kinetics of racemic (anti)adrenergic drugs by the organic cation transporters OCT1 (wild-type and allelic variants), OCT2, OCT3, MATE1, and MATE2-K with a focus on stereospecificity. OCT1 showed stereoselective uptake with up to 2-fold higher vmax over their corresponding counterpart enantiomers for (R,R)-fenoterol, (R,R)-formoterol, (S)-salbutamol, (S)-acebutolol, and (S)-atenolol. Orciprenaline and etilefrine were also transported stereoselectively. The Km was 2.1-fold and 1.5-fold lower for the (S,S)-enantiomers of fenoterol and formoterol, while no significant difference in Km was seen for the other aforementioned drugs. Common OCT1 variants showed similar enantiopreference to wild-type OCT1, with a few notable exceptions (e.g. a switch in enantiospecificity for fenoterol in OCT1 2 compared to the wild-type). Other cation transporters showed strong differences to OCT1 in stereoselectivity and transport activity: The closely related OCT2 displayed a 20-fold higher vmax for (S,S)-fenoterol compared to (R,R)-fenoterol and OCT2 and OCT3 showed 3.5-fold and 4.6-fold higher vmax for the pharmacologically active (R)-salbutamol over (S)-salbutamol. MATE1 and MATE2-K generally mediated transport with a higher capacity but lower affinity compared to OCT1, with moderate stereoselectivity. Our kinetic studies showed that significant stereoselectivity exists in solute carrier-mediated membrane transport of racemic beta-adrenergic drugs with surprising, and in some instances even opposing, preferences between closely related organic cation transporters. This may be relevant for drug therapy, given the strong involvement of these transporters in hepatic and renal drug elimination."],["dc.identifier.doi","10.1016/j.bcp.2019.113731"],["dc.identifier.pmid","31783011"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/68028"],["dc.language.iso","en"],["dc.relation.eissn","1873-2968"],["dc.relation.issn","0006-2952"],["dc.relation.orgunit","Institut für Klinische Pharmakologie"],["dc.title","Stereoselective cell uptake of adrenergic agonists and antagonists by organic cation transporters"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2762"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of Medicinal Chemistry"],["dc.bibliographiccitation.lastpage","2776"],["dc.bibliographiccitation.volume","64"],["dc.contributor.author","Jensen, Ole"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Dücker, Christof"],["dc.date.accessioned","2021-04-14T08:28:43Z"],["dc.date.available","2021-04-14T08:28:43Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1021/acs.jmedchem.0c02047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82691"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1520-4804"],["dc.relation.issn","0022-2623"],["dc.title","Identification of Novel High-Affinity Substrates of OCT1 Using Machine Learning-Guided Virtual Screening and Experimental Validation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","190"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Clinical Pharmacology and Therapeutics"],["dc.bibliographiccitation.lastpage","200"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Matthaei, Johannes"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Jensen, Ole"],["dc.contributor.author","Tann, Annabelle"],["dc.contributor.author","Prukop, Thomas"],["dc.contributor.author","Tadjerpisheh, Sina"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Tzvetkov, Mladen V."],["dc.date.accessioned","2019-10-10T07:11:32Z"],["dc.date.available","2019-10-10T07:11:32Z"],["dc.date.issued","2019"],["dc.description.abstract","Cycloguanil, the active metabolite of proguanil, acts on malaria schizonts in erythrocytes and hepatocytes. We analyzed the impact of the organic cation transporter OCT1 on hepatocellular uptake and pharmacokinetics of proguanil and cycloguanil. OCT1 transported both proguanil and cycloguanil. Common variants OCT1 3 and OCT1 4 caused a substantial decrease and OCT1 5 and OCT1 6 complete abolishment of proguanil uptake. In 39 healthy subjects, low-activity variants OCT1 3 and OCT1 4 had only minor effects on proguanil pharmacokinetics. However, both, cycloguanil area under the time-concentration curve and the cycloguanil-to-proguanil ratio were significantly dependent on number of these low-functional alleles (P = 0.02 for both). Together, CYP2C19, CYP3A5, OCT1 polymorphisms, and sex accounted for 61% of the variation in the cycloguanil-to-proguanil ratio. Most importantly, in vitro OCT1 inhibition caused a fivefold decrease of intracellular cycloguanil concentrations in primary human hepatocytes. In conclusion, OCT1-mediated uptake is a limiting step in bioactivation of proguanil, and OCT1 polymorphisms may affect proguanil efficacy against hepatic malaria schizonts."],["dc.identifier.doi","10.1002/cpt.1128"],["dc.identifier.pmid","29882324"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62483"],["dc.language.iso","en"],["dc.relation.eissn","1532-6535"],["dc.relation.issn","0009-9236"],["dc.title","OCT1 Deficiency Affects Hepatocellular Concentrations and Pharmacokinetics of Cycloguanil, the Active Metabolite of the Antimalarial Drug Proguanil"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","108283"],["dc.bibliographiccitation.firstpage","108283"],["dc.bibliographiccitation.journal","Pharmacology & Therapeutics"],["dc.bibliographiccitation.volume","239"],["dc.contributor.author","Sachkova, Alexandra"],["dc.contributor.author","Jensen, Ole"],["dc.contributor.author","Dücker, Christof"],["dc.contributor.author","Ansari, Salim"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.date.accessioned","2022-12-01T08:30:42Z"],["dc.date.available","2022-12-01T08:30:42Z"],["dc.date.issued","2022"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100001659 Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.1016/j.pharmthera.2022.108283"],["dc.identifier.pii","S0163725822001772"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/117956"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.issn","0163-7258"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","The mystery of the human proton-organic cation antiporter: One transport protein or many?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]