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Membrane transporters in drug development
TLDR
Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions, as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labelling.
Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance.
TLDR
Because of its function in the terminal excretion of cytotoxic and carcinogenic substances, MRP2 as well as other members of the MRP family, play an important role in detoxification and chemoprevention.
Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells.
TLDR
The cloned MRP2 (symbol ABCC2), a MRP family member localized to the apical membrane of polarized cells, demonstrates that MRP 2 confers resistance to cytotoxic drugs.
Localization and Genomic Organization of a New Hepatocellular Organic Anion Transporting Polypeptide*
TLDR
Human OATP8 is a new uptake transporter in the basolateral hepatocyte membrane with an overlapping but distinct substrate specificity as compared with OATp2, which is localized to the same membrane domain.
A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane.
TLDR
The results indicate that OATP2 is important for the uptake of organic anions, including bilirubin conjugates and sulfobromophthalein, in human liver.
The Multidrug Resistance Protein 5 Functions as an ATP-dependent Export Pump for Cyclic Nucleotides*
TLDR
Evidence is provided that cyclic nucleotides are physiological substrates for MRP5 and may represent a novel pharmacological target for the enhancement of tissue levels of cGMP.
Hepatic Uptake of Bilirubin and Its Conjugates by the Human Organic Anion Transporter SLC21A6*
TLDR
Human OATP2 may play a key role in the prevention of hyperbilirubinemia by facilitating the selective entry of unconjugated bilirubin and its glucuronate conjugates into human hepatocytes.
cDNA Cloning of the Hepatocyte Canalicular Isoform of the Multidrug Resistance Protein, cMrp, Reveals a Novel Conjugate Export Pump Deficient in Hyperbilirubinemic Mutant Rats*
TLDR
The results identify cMrp as a canalicular transport protein with a novel sequence and with a function similar to the one of the MRP.
Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane
TLDR
It is found that MRP4 can mediate the efflux of GSH from hepatocytes into blood by cotransport with monoanionic bile salts and may function as an overflow pathway during impaired bile salt secretion across the canalicular membrane into bile.
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