Biomaterial Database

Structural determinants of inhibitor interaction with the human organic cation transporter OCT2 (SLC22A2). 2009

Oliver Zolk, and Thomas F Solbach, and Jörg König, and Martin F Fromm

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Fahrstr. 17, 91054, Erlangen, Germany. zolk@pharmakologie.uni-erlangen.de

The organic cation transporter 2 (OCT2) provides an important pathway for the uptake of cationic compounds in the kidney, which is the essential step in their elimination from the organism. Although many drugs have been identified which interact with human OCT2, structural elements required for an interaction with OCT2 are not well defined. To address this issue, HEK293 cells stably expressing human OCT2 were generated. IC(50) values of commonly used drugs for inhibition of [(3)H]MPP(+) uptake were determined and correlated with physicochemical descriptors. We found only a significant correlation between the topological polar surface area (TPSA) and IC(50) values (r = 0.71, p < 0.0001). Structural alignment of most potent inhibitor drugs of OCT2-mediated MPP(+) uptake was used to construct a two-point pharmacophore consisting of an ion-pair interaction site and a hydrophobic aromatic site separated by 5.0 A. Taken together, our data identify structural determinants for inhibitor interactions with OCT2.

UI	MeSH Term	Description	Entries
D008687	Metformin	A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)	Dimethylguanylguanidine,Dimethylbiguanidine,Glucophage,Metformin HCl,Metformin Hydrochloride,HCl, Metformin,Hydrochloride, Metformin
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D004364	Pharmaceutical Preparations	Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.	Drug,Drugs,Pharmaceutical,Pharmaceutical Preparation,Pharmaceutical Product,Pharmaceutic Preparations,Pharmaceutical Products,Pharmaceuticals,Preparations, Pharmaceutical,Preparation, Pharmaceutical,Preparations, Pharmaceutic,Product, Pharmaceutical,Products, Pharmaceutical
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000075102	Organic Cation Transporter 2	Organic cation transporter consisting of twelve transmembrane domains and expressed primarily in the kidney. It transports a wide range of metabolites, drugs, and neurotransmitters from the blood to the KIDNEY TUBULES, including DOPAMINE; SEROTONIN; CHOLINE; and CISPLATIN.	OCT2 Protein,SLC22A2 Protein,Solute Carrier Family 22 Member 2
D001692	Biological Transport	The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.	Transport, Biological,Biologic Transport,Transport, Biologic
D012995	Solubility	The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Solubilities