Affinage

SLCO1A2

Solute carrier organic anion transporter family member 1A2 · UniProt P46721

Length
670 aa
Mass
74.1 kDa
Annotated
2026-04-28
100 papers in source corpus 15 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLCO1A2 encodes OATP1A2, a sodium-independent multispecific organic anion transporter that mediates cellular influx of a structurally diverse array of amphipathic substrates including bile salts, steroid conjugates (estrone-3-sulfate, DHEAS), drugs (fexofenadine, saquinavir, imatinib, methotrexate, paclitaxel, docetaxel, triptans, aliskiren), and peptide neurotransmitters (substance P) (PMID:10421612, PMID:15832500, PMID:23243220, PMID:25132355). The transporter is expressed at the blood–brain barrier, apical membranes of intestinal enterocytes, renal distal nephron, retinal neurons, and placental syncytiotrophoblasts, where its broad substrate profile supports drug absorption, hepatic clearance, and neurotransmitter reuptake (PMID:15632119, PMID:25132355, PMID:22203093, PMID:24825069). Transcription of SLCO1A2 is upregulated by the vitamin D receptor through a VDRE in the promoter, and under androgen-depleted conditions in prostate cancer cells OATP1A2 imports DHEAS to sustain cell growth (PMID:22474172, PMID:22864060). Naturally occurring nonsynonymous variants impair transport function by reducing plasma membrane trafficking through mechanisms involving altered glycosylation and charge-dependent structural destabilization (PMID:15632119, PMID:23918469).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1999 High

    Establishing OATP1A2 as a drug uptake transporter: the first demonstration that the previously cloned OATP-A mediates cellular influx of a clinically used drug (fexofenadine), showing it functions as a counterpart to P-glycoprotein-mediated efflux.

    Evidence Recombinant vaccinia expression system with radiolabeled fexofenadine uptake and pharmacological inhibition

    PMID:10421612

    Open questions at the time
    • Substrate specificity beyond fexofenadine was unknown
    • Tissue-level relevance of OATP1A2-mediated fexofenadine uptake not addressed
  2. 2003 High

    Broadening substrate scope to endogenous compounds: demonstration that OATP1A2 transports unconjugated bilirubin and identification of its mRNA in liver, placenta, and trophoblast cells extended its potential physiological roles beyond drug transport.

    Evidence Xenopus laevis oocyte expression with radiolabeled bilirubin uptake; RT-PCR in human tissues

    PMID:12568656

    Open questions at the time
    • Bilirubin transport efficiency was very low compared to OATP1B1/1B3, questioning physiological relevance
    • Placental function of OATP1A2 not directly tested
  3. 2004 High

    Defining OATP1A2 as an HIV protease inhibitor transporter: reconstitution in Xenopus oocytes showed saturable saquinavir uptake (Km ~36 µM) and competition by known OATP substrates, establishing OATP1A2 in vectorial hepatic drug transport alongside efflux pumps.

    Evidence Xenopus oocyte expression; HepG2 cell uptake with competitive inhibition

    PMID:15832500

    Open questions at the time
    • In vivo contribution of OATP1A2 to saquinavir pharmacokinetics not demonstrated
    • Relative contribution vs. other OATPs not resolved
  4. 2005 High

    Linking genetic variants to loss of function and revealing the membrane-trafficking mechanism: naturally occurring SNPs (E172D, N135I) drastically reduced transport of estrone-3-sulfate and opioid peptides by impairing plasma membrane localization, with N135I also altering glycosylation, establishing that surface trafficking is rate-limiting for OATP1A2 activity.

    Evidence Transfected cell transport assays; cell surface biotinylation; confocal microscopy; SDS-PAGE glycosylation analysis; immunohistochemistry in brain and kidney

    PMID:15632119

    Open questions at the time
    • Structural basis for how these mutations disrupt folding/trafficking was not resolved at atomic level
    • Clinical pharmacogenomic impact of these SNPs was not assessed
  5. 2011 Medium

    Expanding the drug substrate portfolio and identifying drug–food interactions: OATP1A2 was shown to transport imatinib, aliskiren, and triptans, with naringin (grapefruit juice component) acting as an OATP1A2 inhibitor explaining reduced oral bioavailability of aliskiren and potentially affecting imatinib uptake.

    Evidence HEK293 transfection uptake assays; pharmacological inhibition with naringin; SAR analysis for triptans; MDCKII polarized monolayer transport; clinical crossover pharmacokinetic study for aliskiren

    PMID:21633340 PMID:22124880 PMID:22509823

    Open questions at the time
    • Relative intestinal contribution of OATP1A2 vs. other uptake/efflux transporters for these drugs not fully delineated
    • Clinical significance of OATP1A2 genetic variants for triptan or imatinib disposition not tested
  6. 2011 Medium

    Placental localization to the syncytiotrophoblast apical membrane was established, and reduced OATP1A2 expression in intrahepatic cholestasis of pregnancy suggested a role in placental bile salt/steroid handling.

    Evidence Immunohistochemistry; Western blotting; real-time PCR in normal vs. ICP placentas

    PMID:22203093

    Open questions at the time
    • No direct functional transport assay performed in placental tissue
    • Causal relationship between OATP1A2 downregulation and ICP pathogenesis not demonstrated
  7. 2012 High

    Identifying transcriptional regulation by VDR: vitamin D3 treatment upregulated OATP1A2 in Caco-2 cells via a VDRE in the SLCO1A2 promoter, confirmed by EMSA, ChIP, mutagenesis, and reporter assays, establishing a direct transcriptional regulatory mechanism for intestinal OATP1A2 expression.

    Evidence siRNA knockdown of VDR; EMSA with VDR-RXRα; ChIP; luciferase reporter with site-directed mutagenesis; Western blotting

    PMID:22474172

    Open questions at the time
    • Whether VDR regulation operates at the BBB or other OATP1A2-expressing tissues is unknown
    • Other transcription factors controlling SLCO1A2 expression not identified
  8. 2012 Medium

    Functional role in prostate cancer biology: OATP1A2 is upregulated in androgen-depleted prostate cancer cells and mediates DHEAS import that supports cell proliferation, as shown by siRNA knockdown abolishing DHEAS-driven growth.

    Evidence qRT-PCR; radiolabeled DHEAS uptake; siRNA knockdown; cell growth assay in LNCaP cells

    PMID:22864060

    Open questions at the time
    • In vivo relevance in castration-resistant prostate cancer not demonstrated
    • Relative contribution of OATP1A2 vs. other OATP family members in tumor DHEAS uptake unclear
  9. 2012 High

    In vivo validation via humanized mice: liver-specific OATP1A2 transgenic mice rescued elevated plasma methotrexate and bilirubin in Oatp1a/1b knockouts and uniquely mediated hepatic paclitaxel uptake, providing the first in vivo genetic evidence for OATP1A2 transport function.

    Evidence Humanized transgenic mouse model with pharmacokinetic analysis and tissue distribution

    PMID:23243220

    Open questions at the time
    • Brain and intestinal in vivo contributions of OATP1A2 not addressed by liver-specific transgene
    • Species differences between mouse and human transport kinetics not fully characterized
  10. 2013 High

    Deeper pharmacogenomic understanding: five additional SLCO1A2 SNPs were shown to impair transport of multiple substrates by reducing membrane expression, with mutagenesis revealing that negative charges at positions 184/185 support trafficking and bulky substitutions at T259 destabilize the protein.

    Evidence HEK-293 transfection; radiolabeled uptake for estrone-3-sulfate, imatinib, methotrexate; surface biotinylation; site-directed mutagenesis; molecular modeling

    PMID:23918469

    Open questions at the time
    • No high-resolution structure to map variant effects
    • Population frequencies and clinical pharmacogenomic consequences of these SNPs not established
  11. 2014 High

    Extending in vivo validation to docetaxel and establishing neuronal roles: OATP1A2 rescued docetaxel clearance in humanized mice; separately, retinal and CNS neuronal expression was demonstrated alongside transport of substance P, suggesting a neurotransmitter reuptake function.

    Evidence Humanized transgenic mouse pharmacokinetics for docetaxel; immunofluorescence double-labeling in retina and brain; functional peptide transport assay

    PMID:24825069 PMID:25132355

    Open questions at the time
    • Neurotransmitter reuptake role inferred from co-localization and in vitro transport — no in vivo neuronal function demonstrated
    • Structural determinants for peptide substrate recognition unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Outstanding questions include the lack of a high-resolution structure, the in vivo physiological importance of OATP1A2 at the blood–brain barrier and in neuronal peptide reuptake, the full spectrum of endogenous substrates, and the clinical pharmacogenomic significance of SLCO1A2 variants across diverse drug classes.
  • No crystal or cryo-EM structure available
  • BBB transport function not directly demonstrated in vivo
  • Endogenous substrate repertoire incompletely defined
  • Clinical pharmacogenomic impact of variants not established in prospective studies

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 12
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-382551 Transport of small molecules 10 R-HSA-9748784 Drug ADME 7
Partners
VDR

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Human OATP1A2 (OATP-A) mediates cellular uptake of fexofenadine, as demonstrated using a recombinant vaccinia expression system; P-glycoprotein was identified as the efflux transporter for the same drug, and several P-gp inhibitors also inhibited OATP. Recombinant vaccinia expression system in cells; radiolabeled substrate uptake assay Drug metabolism and disposition High 10421612
2004 OATP1A2 (OATP-A/SLC21A3) mediates influx transport of saquinavir (HIV protease inhibitor) in Xenopus laevis oocytes injected with OATP-A cRNA, with saturable kinetics (Km = 36.4 µM); in HepG2 hepatic cells, OATP-A substrates competitively inhibited saquinavir uptake, indicating OATP-A acts in concert with apical P-gp and MRP2 for vectorial hepatic transport. Xenopus laevis oocyte expression system; HepG2 cell uptake assays with pharmacological inhibitors; saturation kinetics Molecular pharmaceutics High 15832500
2005 OATP1A2 is expressed in human brain capillary endothelial cells and renal distal nephron as demonstrated by immunohistochemistry. Naturally occurring nonsynonymous SNPs in SLCO1A2 (A516C/E172D and A404T/N135I) markedly reduced transport of estrone 3-sulfate, deltorphin II, and DPDPE; reduced plasma membrane expression contributed to loss of function as shown by cell surface biotinylation and confocal microscopy. The A404T variant also showed altered glycosylation. Immunohistochemistry; in vitro transport assays in transfected cells; cell surface biotinylation; immunofluorescence confocal microscopy; SDS-PAGE for glycosylation analysis The Journal of biological chemistry High 15632119
2003 OATP1A2 (OATP-A) mRNA was identified in human liver, placenta, and purified trophoblast cells by RT-PCR and sequencing; injection of OATP-A mRNA into Xenopus laevis oocytes conferred ability to take up unconjugated bilirubin (UCB), though with very low efficiency compared to OATP-8 and OATP-C. RT-PCR/sequencing; real-time quantitative RT-PCR; Xenopus laevis oocyte expression with radiolabeled substrate uptake and kinetic analysis The Biochemical journal High 12568656
2012 Liver-specific humanized OATP1A2 transgenic mice showed partial rescue of increased plasma bilirubin and increased plasma levels of methotrexate seen in Slco1a/1b knockout mice; OATP1A2 (but not OATP1B1) significantly increased liver uptake of paclitaxel (2 mg/kg), demonstrating in vivo transport function of OATP1A2 for both organic anionic (methotrexate) and hydrophobic bulky (paclitaxel) substrates. Humanized transgenic mouse model (liver-specific OATP1A2 knockin in Slco1a/1b knockout background); pharmacokinetic analysis; tissue distribution measurement Clinical cancer research High 23243220
2011 Imatinib uptake was significantly enhanced in OATP1A2-transfected HEK293 cells; naringin (an OATP1A2 inhibitor) decreased imatinib transport in OATP1A2-transfected HEK293 cells, human intestinal Caco-2 cells, and K562 CML cells, establishing OATP1A2 as a transporter of imatinib into cells. HEK293 transfection uptake assay; pharmacological inhibition with naringin in multiple cell lines Clinical pharmacology and therapeutics Medium 21633340
2012 OATP1A2 mRNA expression was most prominently upregulated in LNCaP prostate cancer cells grown under androgen-depleted conditions; DHEAS uptake characteristics in LNCaP cells were consistent with OATP-mediated transport, and siRNA knockdown of OATP1A2 abolished the growth-stimulatory effect of DHEAS, demonstrating a functional role for OATP1A2 in importing DHEAS to support androgen-depleted prostate cancer cell growth. qRT-PCR; radiolabeled DHEAS uptake assay; siRNA knockdown; cell growth assay Biochemical pharmacology Medium 22864060
2012 The SLCO1A2 gene is transactivated by the vitamin D receptor (VDR): treatment of Caco-2 cells with vitamin D3 increased OATP1A2 mRNA and protein; siRNA knockdown of VDR significantly reduced this induction; a VDR response element (VDRE) in SLCO1A2 promoter variant 1 was confirmed by DNase I footprinting-equivalent in silico prediction, electrophoretic mobility shift assay with recombinant VDR-RXRα, luciferase reporter assays, site-directed mutagenesis abolishing activation, and chromatin immunoprecipitation in living cells. siRNA knockdown; RT-PCR; Western blotting; luciferase reporter assay; site-directed mutagenesis; EMSA; chromatin immunoprecipitation (ChIP) Molecular pharmacology High 22474172
2013 Five novel nonsynonymous SNPs in SLCO1A2 (E184K, D185N, T259P, D288N) were identified and shown to impair estrone-3-sulfate, imatinib, and methotrexate transport (~20–50% of wild-type) in HEK-293 cells; biotinylation assays demonstrated impaired plasma membrane expression for these variants; mutagenesis experiments showed that negative charges at positions 184, 185 support membrane targeting, while bulky substitutions at T259 disrupted transporter stability. HEK-293 cell transfection; radiolabeled substrate uptake assay; surface biotinylation; site-directed mutagenesis; molecular modeling The AAPS journal High 23918469
2011 OATP1A2 inhibition by naringin (a grapefruit juice component) was identified as a mechanism for grapefruit juice reduction of aliskiren plasma exposure; in vitro, OATP1A2-expressing HEK293 cells showed linear uptake of [14C]aliskiren that was inhibited by naringin (IC50 75.5 µM), while OATP2B1 did not mediate aliskiren transport. HEK293 transfected cell uptake assay; pharmacological inhibition; human crossover pharmacokinetic study European journal of clinical pharmacology Medium 22124880
2014 OATP1A2 protein is expressed in retinal photoreceptor bodies and somas of amacrine cells, and in neurons and neuronal processes of human cortex, cerebellum, and hippocampus, as shown by immunofluorescence. Substance P and vasoactive intestinal peptide were identified as substrates for OATP1A2 by transport assay, and double-labeling immunofluorescence showed co-expression of OATP1A2 and substance P in the same retinal neurons, suggesting a role in reuptake of peptide neurotransmitters. Immunofluorescence localization; double-labeling immunofluorescence; functional transport assay for peptide substrates Pflugers Archiv : European journal of physiology Medium 25132355
2012 Hydrophilic triptans (5-HT1B/1D receptor agonists) are substrates for OATP1A2 as established in a BacMam2-OATP1A2 transduced HEK293 system; kinetics (Km and Vmax) were determined for six marketed triptans. Structure-activity relationship analysis revealed that a positively charged basic amine atom is essential for efficient OATP1A2-mediated triptan uptake; OATP1A2 expressed on the apical side of MDCKII monolayers facilitated apical-to-basolateral transport of triptans. BacMam2-transduced HEK293 cells; radiolabeled and unlabeled uptake assays; kinetic analysis; SAR with structural analogs; MDCKII polarized transport assay Xenobiotica Medium 22509823
2014 Liver-specific humanized OATP1A2 transgenic mice showed nearly complete rescue of increased plasma levels of docetaxel observed in Oatp1a/1b-null mice after intravenous administration, demonstrating that OATP1A2 can mediate in vivo hepatic uptake and clearance of docetaxel. Humanized transgenic mouse model (liver-specific OATP1A2 knockin in Slco1a/1b knockout background); pharmacokinetic analysis; tissue distribution measurement International journal of cancer High 24825069
2015 All 11 human OATPs including OATP1A2 were functionally expressed in the baculovirus-Sf9 insect cell system; OATP1A2 was shown to transport sodium fluorescein and fluorescein-methotrexate, and OATP1A2 also transported imatinib; acidic extracellular pH greatly facilitated fluorescein uptake by all OATPs. Baculovirus-Sf9 insect cell expression; fluorescence-based uptake assay; inhibition studies; pH dependency assay Biochemical pharmacology Medium 26415544
2011 OATP1A2 protein is expressed in human placenta and is localized to the vasculo-syncytial membrane (VSM) and apical surface of syncytiotrophoblasts as determined by immunohistochemistry; OATP1A2 mRNA and protein expression were significantly lower in placentas from intrahepatic cholestasis of pregnancy (ICP) compared to normal placentas. Real-time PCR; Western blotting; immunohistochemistry Archives of gynecology and obstetrics Medium 22203093

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Impact of OATP transporters on pharmacokinetics. British journal of pharmacology 741 19785645
2003 Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers Archiv : European journal of physiology 709 14579113
2001 Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology 566 11159893
2000 Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochemical and biophysical research communications 493 10873595
2001 Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. The Journal of biological chemistry 486 11477075
1999 OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug metabolism and disposition: the biological fate of chemicals 476 10421612
2003 Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics. Clinical pharmacology and therapeutics 396 12811365
2004 High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1). Pharmacogenetics 341 15226675
2005 Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells. Pharmacogenetics and genomics 305 15970799
2008 Xenobiotic transporters of the human organic anion transporting polypeptides (OATP) family. Xenobiotica; the fate of foreign compounds in biological systems 303 18668430
2005 Polymorphisms in human organic anion-transporting polypeptide 1A2 (OATP1A2): implications for altered drug disposition and central nervous system drug entry. The Journal of biological chemistry 283 15632119
2006 Pharmacogenomics of human OATP transporters. Naunyn-Schmiedeberg's archives of pharmacology 270 16525793
2002 Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis. The Journal of pharmacology and experimental therapeutics 255 12130747
2004 Evidence for inverse effects of OATP-C (SLC21A6) 5 and 1b haplotypes on pravastatin kinetics. Clinical pharmacology and therapeutics 229 15116054
2007 Role of OATP transporters in the disposition of drugs. Pharmacogenomics 194 18240907
2005 Molecular mechanisms of reduced glutathione transport: role of the MRP/CFTR/ABCC and OATP/SLC21A families of membrane proteins. Toxicology and applied pharmacology 182 15845416
2005 Contribution of OATP (organic anion-transporting polypeptide) family transporters to the hepatic uptake of fexofenadine in humans. Drug metabolism and disposition: the biological fate of chemicals 159 16014768
2010 The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro: a comparison of primary human hepatocytes and OATP-transfected HEK293 cells. Toxicology and applied pharmacology 148 20171238
2003 Organic anion-transporting polypeptide (OATP) transporter family and drug disposition. European journal of clinical investigation 142 14641549
2006 Predominant contribution of organic anion transporting polypeptide OATP-B (OATP2B1) to apical uptake of estrone-3-sulfate by human intestinal Caco-2 cells. Drug metabolism and disposition: the biological fate of chemicals 135 16714376
2003 Role of organic anion-transporting polypeptides, OATP-A, OATP-C and OATP-8, in the human placenta-maternal liver tandem excretory pathway for foetal bilirubin. The Biochemical journal 133 12568656
2004 The organic anion transporter (OATP) family. Drug metabolism and pharmacokinetics 127 15499184
2002 Characterization of an organic anion-transporting polypeptide (OATP-B) in human placenta. The Journal of clinical endocrinology and metabolism 127 11932330
2005 Flavonoids as a novel class of human organic anion-transporting polypeptide OATP1B1 (OATP-C) modulators. Drug metabolism and disposition: the biological fate of chemicals 124 16081670
2004 Functional analysis of single nucleotide polymorphisms of hepatic organic anion transporter OATP1B1 (OATP-C). Pharmacogenetics 124 15564882
2001 Characterization of the human OATP-C (SLC21A6) gene promoter and regulation of liver-specific OATP genes by hepatocyte nuclear factor 1 alpha. The Journal of biological chemistry 119 11483603
2008 Oatp-associated uptake and toxicity of microcystins in primary murine whole brain cells. Toxicology and applied pharmacology 114 19027771
2012 Influence of human OATP1B1, OATP1B3, and OATP1A2 on the pharmacokinetics of methotrexate and paclitaxel in humanized transgenic mice. Clinical cancer research : an official journal of the American Association for Cancer Research 112 23243220
2011 Oral drug delivery utilizing intestinal OATP transporters. Advanced drug delivery reviews 112 21824501
2018 Apple-Derived Nanoparticles Modulate Expression of Organic-Anion-Transporting Polypeptide (OATP) 2B1 in Caco-2 Cells. Molecular pharmaceutics 107 30359033
2011 Uptake transporters of the human OATP family: molecular characteristics, substrates, their role in drug-drug interactions, and functional consequences of polymorphisms. Handbook of experimental pharmacology 107 21103967
2003 Oxidized ATP (oATP) attenuates proinflammatory signaling via P2 receptor-independent mechanisms. British journal of pharmacology 107 14522842
2006 Organic anion transporting polypeptides of the OATP/SLCO superfamily: identification of new members in nonmammalian species, comparative modeling and a potential transport mode. The Journal of membrane biology 102 16648940
2004 Effect of genetic polymorphism of OATP-C (SLCO1B1) on lipid-lowering response to HMG-CoA reductase inhibitors. Drug metabolism and pharmacokinetics 97 15548849
2004 Human organic anion-transporting polypeptide OATP-A (SLC21A3) acts in concert with P-glycoprotein and multidrug resistance protein 2 in the vectorial transport of Saquinavir in Hep G2 cells. Molecular pharmaceutics 94 15832500
2006 SLCO/OATP-like transport of glutathione in FasL-induced apoptosis: glutathione efflux is coupled to an organic anion exchange and is necessary for the progression of the execution phase of apoptosis. The Journal of biological chemistry 92 16857677
2011 Expression of OATP family members in hormone-related cancers: potential markers of progression. PloS one 91 21625523
2011 Genetic polymorphisms of OATP transporters and their impact on intestinal absorption and hepatic disposition of drugs. Drug metabolism and pharmacokinetics 91 22185815
2004 Pharmacogenomics of the OATP and OAT families. Pharmacogenomics 87 15102542
1996 Transient expression of oatp organic anion transporter in mammalian cells: identification of candidate substrates. The American journal of physiology 85 8779893
1997 Expression of the liver Na+-independent organic anion transporting polypeptide (oatp-1) in rats with bile duct ligation. Journal of hepatology 81 9453431
2018 Regulation of Organic Anion Transporting Polypeptides (OATP) 1B1- and OATP1B3-Mediated Transport: An Updated Review in the Context of OATP-Mediated Drug-Drug Interactions. International journal of molecular sciences 80 29538325
2014 Differential cellular expression of organic anion transporting peptides OATP1A2 and OATP2B1 in the human retina and brain: implications for carrier-mediated transport of neuropeptides and neurosteriods in the CNS. Pflugers Archiv : European journal of physiology 80 25132355
2009 Organic anion transporting polypeptide (Oatp) 1a1-mediated perfluorooctanoate transport and evidence for a renal reabsorption mechanism of Oatp1a1 in renal elimination of perfluorocarboxylates in rats. Toxicology letters 80 19616083
2003 Semi quantitative expression analysis of MDR3, FIC1, BSEP, OATP-A, OATP-C,OATP-D, OATP-E and NTCP gene transcripts in 1st and 3rd trimester human placenta. Placenta 80 12495658
2003 Molecular characterization of human and rat organic anion transporter OATP-D. American journal of physiology. Renal physiology 78 14631946
1996 Estradiol 17 beta-D-glucuronide is a high-affinity substrate for oatp organic anion transporter. The American journal of physiology 78 8779894
2013 Utility of Oatp1a/1b-knockout and OATP1B1/3-humanized mice in the study of OATP-mediated pharmacokinetics and tissue distribution: case studies with pravastatin, atorvastatin, simvastatin, and carboxydichlorofluorescein. Drug metabolism and disposition: the biological fate of chemicals 77 24194513
2012 Characterization of organic anion transporting polypeptide (OATP) expression and its functional contribution to the uptake of substrates in human hepatocytes. Molecular pharmaceutics 77 23082789
2008 Pharmacogenetics of OATP (SLC21/SLCO), OAT and OCT (SLC22) and PEPT (SLC15) transporters in the intestine, liver and kidney. Pharmacogenomics 76 18466105
2001 Expression of hepatic transporters OATP-C and MRP2 in primary sclerosing cholangitis. Liver 75 11454187
2015 Meta-analysis of expression of hepatic organic anion-transporting polypeptide (OATP) transporters in cellular systems relative to human liver tissue. Drug metabolism and disposition: the biological fate of chemicals 70 25564656
2011 The analysis of organic anion transporting polypeptide (OATP) mRNA and protein patterns in primary and metastatic liver cancer. Cancer biology & therapy 69 21383546
2017 Effect of Chronic Kidney Disease on Nonrenal Elimination Pathways: A Systematic Assessment of CYP1A2, CYP2C8, CYP2C9, CYP2C19, and OATP. Clinical pharmacology and therapeutics 68 28990182
2003 Expression of organic anion transporting polypeptide E (OATP-E) in human placenta. Placenta 68 12566240
1996 Regulation of renal oatp mRNA expression by testosterone. The American journal of physiology 66 8779895
2006 Uptake of ursodeoxycholate and its conjugates by human hepatocytes: role of Na(+)-taurocholate cotransporting polypeptide (NTCP), organic anion transporting polypeptide (OATP) 1B1 (OATP-C), and oatp1B3 (OATP8). Molecular pharmaceutics 59 16686371
2004 A novel variant allele of OATP-C (SLCO1B1) found in a Japanese patient with pravastatin-induced myopathy. Drug metabolism and pharmacokinetics 59 15681900
2011 Pharmacokinetic impact of SLCO1A2 polymorphisms on imatinib disposition in patients with chronic myeloid leukemia. Clinical pharmacology and therapeutics 58 21633340
2011 Digoxin is not a substrate for organic anion-transporting polypeptide transporters OATP1A2, OATP1B1, OATP1B3, and OATP2B1 but is a substrate for a sodium-dependent transporter expressed in HEK293 cells. Drug metabolism and disposition: the biological fate of chemicals 58 21849517
2008 Altered expression of organic anion transporter polypeptide (OATP) genes in human breast carcinoma. Cancer biology & therapy 58 18948755
2009 In vitro evidence for the role of OATP and OCT uptake transporters in drug-drug interactions. Expert opinion on drug metabolism & toxicology 56 19416085
2012 Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions. Biochemical pharmacology 54 22864060
2016 Investigation of Fluorescein Derivatives as Substrates of Organic Anion Transporting Polypeptide (OATP) 1B1 To Develop Sensitive Fluorescence-Based OATP1B1 Inhibition Assays. Molecular pharmaceutics 50 26696140
2014 Human OATP1B1, OATP1B3 and OATP1A2 can mediate the in vivo uptake and clearance of docetaxel. International journal of cancer 50 24825069
2013 Effects of selected OATP and/or ABC transporter inhibitors on the brain and whole-body distribution of glyburide. The AAPS journal 50 23907487
2009 Organic anion transporting polypeptides (OATP) in zebrafish (Danio rerio): Phylogenetic analysis and tissue distribution. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 50 19931635
2008 Critical role of PPAR-alpha in perfluorooctanoic acid- and perfluorodecanoic acid-induced downregulation of Oatp uptake transporters in mouse livers. Toxicological sciences : an official journal of the Society of Toxicology 50 18703564
2013 OATP transporter-mediated drug absorption and interaction. Current opinion in pharmacology 49 24060700
2006 The role of STS and OATP-B mRNA expression in predicting the clinical outcome in human breast cancer. Anticancer research 49 17214375
2011 Determination of OATP-, NTCP- and OCT-mediated substrate uptake activities in individual and pooled batches of cryopreserved human hepatocytes. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 48 21605667
2011 Intestinal OATP1A2 inhibition as a potential mechanism for the effect of grapefruit juice on aliskiren pharmacokinetics in healthy subjects. European journal of clinical pharmacology 48 22124880
2011 Pharmacogenetics of OATP transporters reveals that SLCO1B1 c.388A>G variant is determinant of increased atorvastatin response. International journal of molecular sciences 47 22016628
2021 HMG-CoA Reductase Inhibitors (Statins) and their Drug Interactions Involving CYP Enzymes, P-glycoprotein and OATP Transporters-An Overview. Current drug metabolism 46 33459228
2017 Transporter-Mediated Alterations in Patients With NASH Increase Systemic and Hepatic Exposure to an OATP and MRP2 Substrate. Clinical pharmacology and therapeutics 46 29271075
2011 OATP 1B1/1B3 expression in hepatocellular carcinomas treated with orthotopic liver transplantation. Virchows Archiv : an international journal of pathology 43 21691816
2020 Effects of Chrysin and Its Major Conjugated Metabolites Chrysin-7-Sulfate and Chrysin-7-Glucuronide on Cytochrome P450 Enzymes and on OATP, P-gp, BCRP, and MRP2 Transporters. Drug metabolism and disposition: the biological fate of chemicals 42 32661014
2013 Evaluation of Oatp and Mrp2 activities in hepatobiliary excretion using newly developed positron emission tomography tracer [11C]dehydropravastatin in rats. The Journal of pharmacology and experimental therapeutics 42 23926287
2006 Endocrine regulation of gender-divergent mouse organic anion-transporting polypeptide (Oatp) expression. Molecular pharmacology 42 16807376
2018 Organic Anion Transporting Polypeptide (OATP) transporter expression, localization and function in the human intestine. Pharmacology & therapeutics 40 30347208
2013 Functional analysis of novel polymorphisms in the human SLCO1A2 gene that encodes the transporter OATP1A2. The AAPS journal 39 23918469
1996 Ontogenic expression of the Na(+)-independent organic anion transporting polypeptide (oatp) in rat liver and kidney. Journal of hepatology 39 9007723
2018 Genetic variability and population diversity of the human SLCO (OATP) transporter family. Pharmacological research 37 30359687
2015 Functional expression of the 11 human Organic Anion Transporting Polypeptides in insect cells reveals that sodium fluorescein is a general OATP substrate. Biochemical pharmacology 37 26415544
2012 The SLCO1A2 gene, encoding human organic anion-transporting polypeptide 1A2, is transactivated by the vitamin D receptor. Molecular pharmacology 37 22474172
2011 The evolution of the OATP hepatic uptake transport protein family in DMPK sciences: from obscure liver transporters to key determinants of hepatobiliary clearance. Xenobiotica; the fate of foreign compounds in biological systems 37 22077101
2022 OAT, OATP, and MRP Drug Transporters and the Remote Sensing and Signaling Theory. Annual review of pharmacology and toxicology 36 36206988
2013 Localization of organic anion transporting polypeptide (Oatp) 1a4 and Oatp1c1 at the rat blood-retinal barrier. Fluids and barriers of the CNS 36 24083450
2012 Whole-body distribution and radiation dosimetry of [11C]telmisartan as a biomarker for hepatic organic anion transporting polypeptide (OATP) 1B3. Nuclear medicine and biology 36 22421430
2004 Influence of common variants in the pharmacokinetic genes (OATP-C, UGT1A1, and MRP2) on serum bilirubin levels in healthy subjects. Hepatology research : the official journal of the Japan Society of Hepatology 36 15519273
2019 Characterization of Plasma Membrane Localization and Phosphorylation Status of Organic Anion Transporting Polypeptide (OATP) 1B1 c.521 T>C Nonsynonymous Single-Nucleotide Polymorphism. Pharmaceutical research 35 31093828
2014 Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of tyrosine kinase inhibitors. Drug metabolism and drug interactions 35 24643910
2012 Hydrophilic anti-migraine triptans are substrates for OATP1A2, a transporter expressed at human blood-brain barrier. Xenobiotica; the fate of foreign compounds in biological systems 34 22509823
2018 Dual-channel fluorescence diagnosis of cancer cells/tissues assisted by OATP transporters and cysteine/glutathione. Chemical science 32 29732104
2010 Mechanism of polybrominated diphenyl ether uptake into the liver: PBDE congeners are substrates of human hepatic OATP transporters. Toxicological sciences : an official journal of the Society of Toxicology 32 20176623
2018 Relative Activity Factor (RAF)-Based Scaling of Uptake Clearance Mediated by Organic Anion Transporting Polypeptide (OATP) 1B1 and OATP1B3 in Human Hepatocytes. Molecular pharmaceutics 31 29746136
2015 Zebrafish Oatp-mediated transport of microcystin congeners. Archives of toxicology 31 26055554
2011 Alteration in placental expression of bile acids transporters OATP1A2, OATP1B1, OATP1B3 in intrahepatic cholestasis of pregnancy. Archives of gynecology and obstetrics 31 22203093
2009 Construction of triple-transfected cells [organic anion-transporting polypeptide (OATP) 1B1/multidrug resistance-associated protein (MRP) 2/MRP3 and OATP1B1/MRP2/MRP4] for analysis of the sinusoidal function of MRP3 and MRP4. Drug metabolism and disposition: the biological fate of chemicals 31 19628752
2006 Evidence of Oatp and Mdr1 in cryopreserved rat hepatocytes. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 30 17174077