Affinage

Showing SLCO1B3 — OATP1B3 is a alias.

SLCO1B3

Solute carrier organic anion transporter family member 1B3 · UniProt Q9NPD5

Length
702 aa
Mass
77.4 kDa
Annotated
2026-06-10
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OATP1B3 (SLCO1B3) is a multispecific, Na+-independent organic anion uptake transporter of the hepatocyte basolateral (sinusoidal) membrane that, together with the apical export pump MRP2/ABCC2, drives vectorial hepatobiliary elimination of its substrates (PMID:11641421, PMID:12695556). Its substrate range is broad and includes bilirubin and bile acid conjugates, steroid hormones such as testosterone, the peptide CCK-8, and numerous drugs including statins, telmisartan, paclitaxel, taxanes, and microcystin-LR (PMID:12568656, PMID:15665139, PMID:16611857, PMID:17186002, PMID:18519758). Substrate selectivity is encoded in discrete structural elements—transmembrane helices 1 and 10 and extracellular loop 6 govern CCK-8 recognition, and individual residue substitutions abolish bile acid transport while sparing other substrates (PMID:15226676, PMID:22352740). In the liver-blood shuttle, OATP1B3 mediates hepatic reuptake of bilirubin conjugates secreted into blood by MRP3/ABCC3; transgenic human OATP1B3 alone rescues bilirubin conjugate clearance in Oatp-deficient mice, and complete combined OATP1B1/OATP1B3 deficiency causes Rotor syndrome (PMID:22232210). Plasma membrane targeting requires the N-terminal 12–28 amino acid region (PMID:28216016). Transport activity is regulated post-translationally by PKC-mediated phosphorylation, which suppresses function without changing surface expression, and by hetero-oligomerization with OCT1, OATP1B1, and NTCP that reciprocally tune membrane abundance and turnover (PMID:25200870, PMID:32482756). SLCO1B3 transcription is repressed by HNF3β/FOXA2 and, in cancer, induced by Wnt/β-catenin and HIF-1α signalling, with additional post-transcriptional control by miR-579-3p (PMID:14739090, PMID:24946283, PMID:23924606, PMID:34031488). A cancer-specific N-terminally truncated variant (Ct-OATP1B3) is cytoplasmic with reduced transport activity but acquires a non-transport function by binding IGF2BP2 to stabilize CPT1A/NDUFA2 mRNAs and reprogram metabolism, promoting cancer cell migration (PMID:23215050, PMID:35717493).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 High

    Establishing that OATP1B3 is a basolateral hepatocyte uptake transporter cooperating with an apical export pump defined its core role in vectorial hepatobiliary elimination.

    Evidence Double-transfected MDCK Transwell transport with OATP1B3 + MRP2, immunofluorescence localization, multiple substrate uptake

    PMID:11641421

    Open questions at the time
    • Did not resolve transport stoichiometry or driving ion
    • Substrate spectrum at this point partial
  2. 2003 Medium

    Localization to the sinusoidal hepatocyte membrane and demonstration of bilirubin/estradiol transport tied OATP1B3 to physiological organic anion and bilirubin handling.

    Evidence Immunofluorescence/IHC on human liver and tumors; Xenopus oocyte kinetic uptake of unconjugated bilirubin

    PMID:12568656 PMID:12695556

    Open questions at the time
    • Tumor expression pattern not mechanistically explained
    • Placental role inferred from mRNA only
  3. 2004 High

    Mutagenesis distinguished trafficking-defective from substrate-selective effects, showing OATP1B3 residues differentially control localization versus transport of specific substrates.

    Evidence Site-directed mutagenesis (G522C, G583E, S112A, M233I) with localization and radiolabeled transport assays in MDCKII/HEK293

    PMID:15226676

    Open questions at the time
    • Structural basis of substrate-selective loss not defined
    • G522C/G583E are rare/artificial mutations
  4. 2004 High

    Identification of HNF3β/FOXA2 as a promoter-binding repressor provided the first transcriptional control mechanism and a link to its loss in HCC.

    Evidence Luciferase reporter, EMSA mapping to -39/-23, clinical HCC correlation

    PMID:14739090

    Open questions at the time
    • Upstream signals controlling HNF3β not addressed
    • Causality in HCC not tested functionally
  5. 2005 High

    Reconstitution of CCK-8 vectorial transport defined a high-affinity peptide substrate and provided the canonical functional reporter used in later mechanistic studies.

    Evidence Double-transfected MDCKII Transwell assay, MRP2 vesicle ATP-dependent transport, cyclosporin A inhibition

    PMID:15665139

    Open questions at the time
    • Physiological significance of hepatic CCK-8 clearance unclear
  6. 2006 Medium

    Expanding the substrate set to multiple drugs and bile acid conjugates and demonstrating GSH-coupled cotransport established OATP1B3 as a broad, possibly bidirectional, anion carrier.

    Evidence HEK293/oocyte/CHO uptake kinetics, human hepatocyte validation, GSH cotransport stoichiometry analysis, EHBR rat in vivo

    PMID:16501004 PMID:16611857 PMID:16686371 PMID:16877380 PMID:17496208

    Open questions at the time
    • Bidirectional/export function shown only in oocytes
    • GSH cotransport not validated in native membrane
  7. 2007 Medium

    Demonstrating selective transport of paclitaxel and active uptake of the toxin microcystin-LR linked OATP1B3 both to chemotherapeutic disposition and to toxin-mediated cell death signalling.

    Evidence Oocyte transporter panel for paclitaxel; HEK293 microcystin-LR uptake with PP2A/MAPK pathway and apoptosis readouts

    PMID:17186002 PMID:17369605

    Open questions at the time
    • Paclitaxel SNP associations negative in patients
    • Microcystin downstream signalling specific to overexpression model
  8. 2008 Medium

    Testosterone transport and its impairment by a common haplotype, plus a transport-dependent antiapoptotic effect in p53-wildtype cancer cells, connected OATP1B3 to hormone handling and chemoresistance.

    Evidence Cos-7 WT vs variant testosterone transport; colorectal cancer overexpression with transport-dead G583E control and p53 reporter/target analysis

    PMID:18519758 PMID:19074900

    Open questions at the time
    • Mechanism linking transport to p53 suppression not defined
    • Haplotype effect not confirmed in vivo here
  9. 2012 High

    Mapping substrate specificity to TM1/TM10/ECL6 and confirming Rotor syndrome via transgenic mouse rescue established both the structural logic of recognition and the in vivo physiological role in bilirubin reuptake.

    Evidence Chimeric/mutant transporter library with gain-of-function CCK-8 transport; Rotor family genetics with Oatp1a/1b-null and OATP1B3-transgenic rescue mice

    PMID:22232210 PMID:22352740

    Open questions at the time
    • No high-resolution structure of the transporter
    • Substrate determinants mapped only for CCK-8
  10. 2012 Medium

    Characterizing the cancer-type variant lacking the first 28 N-terminal residues as cytoplasmic and transport-impaired set up a distinct, non-canonical role for OATP1B3 in tumors.

    Evidence RT-PCR variant identification, subcellular fractionation, CCK-8 transport, proteasome inhibitor treatment in HEK293T

    PMID:23215050

    Open questions at the time
    • Function of cytoplasmic variant not yet defined at this stage
    • Truncation origin (splicing) mechanism not detailed here
  11. 2013 Medium

    Identifying Wnt/β-catenin and HIF-1α as cancer-context inducers and a sorafenib-glucuronide substrate role expanded the regulatory and pharmacologic picture in tumors.

    Evidence LiCl Wnt activation + HCC correlation; HIF-1α HRE reporter/EMSA/siRNA on cancer-specific promoter; HEK293 transport + Oatp1b2-null/transgenic mouse PK for sorafenib-glucuronide

    PMID:23340295 PMID:23924606 PMID:24946283

    Open questions at the time
    • Wnt-to-promoter signalling steps not fully traced
    • Cancer-specific vs liver-type promoter usage requires further dissection
  12. 2014 High

    Demonstrating PKC-mediated phosphorylation that suppresses activity without altering surface expression revealed acute post-translational control of transport function.

    Evidence Sandwich-cultured human hepatocytes, surface biotinylation, anti-phospho IP, CCK-8 assay, PKC inhibitor BIM I

    PMID:25200870

    Open questions at the time
    • Specific phosphorylated residues not mapped
    • Physiological trigger of PKC regulation unknown
  13. 2014 Medium

    Showing β-islet expression and glibenclamide transport that enhances insulinotropic effect extended OATP1B3 function beyond liver to tissue-level drug action.

    Evidence MDCKII transport, CCK-8 inhibition, MIN6 overexpression with insulin secretion assay

    PMID:24150606

    Open questions at the time
    • Endogenous β-cell expression level/relevance not quantified
    • Single rodent β-cell model
  14. 2016 Medium

    Bidirectional manipulation in prostate cancer models established that loss of SLCO1B3 reduces intratumoural taxane levels and drives resistance.

    Evidence PDX and PC346C models, siRNA knockdown and overexpression, [14C]-docetaxel/cabazitaxel uptake and cytotoxicity

    PMID:27537383

    Open questions at the time
    • Regulatory cause of expression loss in resistant tumors not defined here
  15. 2017 High

    Defining the N-terminal 12-28 region as required for membrane trafficking and quantifying testosterone uptake in vivo linked transporter localization, androgen disposition, and prostate cancer biology.

    Evidence N-terminal truncation/fusion mutants with fractionation in three cell lines; inducible cell kinetics and Slco1b2-/-/hSLCO1B3 knock-in mouse testosterone PK; CRPC siRNA

    PMID:28216016 PMID:28389619

    Open questions at the time
    • Trafficking machinery recognizing the N-terminus not identified
    • Mechanism of CRPC upregulation not resolved here
  16. 2020 Medium

    Demonstrating hetero-oligomerization with OCT1, OATP1B1, and NTCP that reciprocally alters membrane expression and turnover revealed transporter-transporter interplay as a functional regulator.

    Evidence Co-IP from human hepatocytes, proximity ligation in liver sections, surface biotinylation, CCK-8 transport, OCT1 knockdown

    PMID:32482756

    Open questions at the time
    • Oligomer interface/stoichiometry not structurally defined
    • Physiological extent of regulation in vivo unclear
  17. 2021 Medium

    Identifying miR-579-3p as a 3'UTR-binding repressor whose abiraterone-induced downregulation upregulates SLCO1B3 added a post-transcriptional layer relevant to prostate cancer therapy.

    Evidence qPCR, NanoString miRNA profiling, dual luciferase 3'UTR reporter, 22Rv1 xenograft

    PMID:34031488

    Open questions at the time
    • Upstream control of miR-579-3p by abiraterone not fully mechanistic
    • Clinical relevance to drug exposure untested
  18. 2022 Medium

    Establishing that the cytoplasmic cancer variant binds IGF2BP2 to stabilize metabolic mRNAs assigned Ct-OATP1B3 a transport-independent moonlighting function driving cancer metabolic reprogramming and invasion.

    Evidence Co-IP, RNA-binding pulldown, mRNA stability and Seahorse metabolic assays, lamellipodia imaging, in vivo metastasis xenograft, siRNA

    PMID:35717493

    Open questions at the time
    • Direct vs indirect binding to CPT1A/NDUFA2 transcripts not resolved
    • Generality beyond ovarian cancer unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure defining the transport mechanism, ion coupling, and the molecular basis of multispecific substrate recognition across the full substrate range remains unestablished.
  • No experimental atomic structure in the corpus
  • Specificity determinants mapped only for CCK-8
  • Coupling ions/driving force not fully defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 9 GO:0140104 molecular carrier activity 3 GO:0003723 RNA binding 1
Localization
GO:0005829 cytosol 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-9748784 Drug ADME 6 R-HSA-1430728 Metabolism 3 R-HSA-382551 Transport of small molecules 3
Partners
ABCC2IGF2BP2SLC10A1SLC22A1SLCO1B1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 OATP1B3 (SLC21A8/OATP8) mediates basolateral uptake of organic anions (BSP, leukotriene C4, 17β-glucuronosyl estradiol, DHEA-S, fluo-3, rifampicin) in hepatocytes; vectorial transcellular transport from basolateral to apical compartment was reconstituted in double-transfected MDCK cells co-expressing OATP1B3 at the basolateral membrane and ABCC2/MRP2 at the apical membrane, demonstrating cooperative hepatobiliary elimination. Double-transfected MDCK cell Transwell transport assay; immunoblotting; confocal laser scanning microscopy for protein localization Molecular pharmacology High 11641421
2003 OATP1B3 (SLC21A8/OATP8) is localized to the basolateral (sinusoidal) membrane of human hepatocytes; both OATP1B3 and OATP1B1 were detected in hepatocellular carcinoma with irregular staining pattern but absent in HepG2 cells and absent in cholangiocarcinoma/colorectal/pancreatic liver metastases. Immunoblot, immunoprecipitation, immunofluorescence microscopy with monoclonal antibodies; immunohistochemistry on paraffin sections of liver tumors Laboratory investigation Medium 12695556
2003 OATP1B3 (OATP-8) transports unconjugated bilirubin (UCB) and 17β-glucuronosyl estradiol in a carrier-mediated, saturable manner when expressed in Xenopus laevis oocytes; OATP1B3 mRNA is expressed in human placental trophoblasts suggesting a role in fetal UCB clearance via the placenta-maternal liver tandem. Xenopus oocyte expression system; radiolabeled substrate uptake assay; RT-PCR and real-time quantitative RT-PCR; kinetic analysis The Biochemical journal Medium 12568656
2004 OATP1B3 mediates Na+-independent, saturable uptake of pitavastatin (Km ~3.3 µM) in HEK293 cells; OATP1B1 accounts for ~90% of total hepatic uptake of pitavastatin in humans based on relative activity factor methodology. Transporter-expressing HEK293 cells; radiolabeled uptake assay; Western blot for relative expression; cryopreserved human hepatocyte uptake assay The Journal of pharmacology and experimental therapeutics Medium 15159445
2004 Mutations in SLCO1B3 have substrate-specific functional consequences: OATP1B3-G522C and OATP1B3-G583E (rare/artificial mutations) are retained intracellularly and abolish bile acid transport but retain transport of BSP; common polymorphisms S112A and M233I show normal lateral membrane localization and comparable transport activity. Site-directed mutagenesis; stable transfection in MDCKII and HEK293 cells; immunofluorescence for localization; radiolabeled substrate transport assays Pharmacogenetics High 15226676
2004 HNF3β (FOXA2) transcriptionally represses the SLCO1B3 (OATP8) gene promoter; an HNF3β binding site was mapped to nucleotides -39/-23 of the OATP8 promoter by EMSA; HNF3β cotransfection reduced OATP8 promoter activity by ~70% in Huh7 cells and inversely correlated with OATP8 mRNA/protein in HCC. Luciferase reporter assay; electrophoretic mobility shift assay (EMSA); real-time PCR; Western blot; correlation analysis in 13 paired HCC/non-tumor liver samples Journal of hepatology High 14739090
2005 OATP1B3 mediates high-affinity, saturable uptake of the peptide CCK-8 (cholecystokinin-8) at the basolateral membrane; vectorial transport of CCK-8 across MDCK cells requires both OATP1B3 (uptake) and ABCC2/MRP2 (apical efflux); MRP2 transports CCK-8 with Km = 8.1 µM in an ATP-dependent manner; cyclosporin A inhibits OATP1B3 uptake (Ki = 1.2 µM). Double-transfected MDCKII Transwell vectorial transport assay; membrane vesicle ATP-dependent transport assay; immunofluorescence microscopy; radiolabeled substrate uptake The Journal of pharmacology and experimental therapeutics High 15665139
2006 OATP1B3 is the predominant transporter for hepatic uptake of telmisartan (Km = 0.81 µM) in humans; OATP1B1-expressing cells showed no significant uptake; selective inhibition with estrone-3-sulfate in human hepatocytes confirmed OATP1B3 predominance. HEK293 cells stably expressing OATP1B1 or OATP1B3; cryopreserved human hepatocyte uptake assay; selective inhibition studies; kinetic analysis Drug metabolism and disposition High 16611857
2006 OATP1B3 mediates Na+-independent, saturable uptake of olmesartan (Km = 71.8 µM) in Xenopus oocytes; OATP1B1 also transports olmesartan (Km = 42.6 µM); biliary excretion is mediated by MRP2 as shown by drastically reduced cumulative biliary excretion in EHBR (mrp2-deficient) rats. Xenopus oocyte expression; radiolabeled transport assay; EHBR rat in vivo model; canalicular membrane vesicle ATP-dependent transport assay; MRP2-expressing vesicles Drug metabolism and disposition Medium 16501004
2006 OATP1B3 transports TUDC and GUDC (bile acid conjugates) but not unconjugated UDCA in HEK293 expression systems; NTCP also transports UDCA and its conjugates; differential Na+-dependent and -independent contributions to hepatic uptake of UDCA conjugates were established. Transporter-expressing HEK293 cells; radiolabeled substrate uptake assay; Na+ replacement experiments; cryopreserved human hepatocyte uptake assays Molecular pharmaceutics Medium 16686371
2006 OATP1B3 (OATP8/1B3) can mediate bile acid efflux in a glutathione-dependent manner: GSH cis-stimulates OATP1B3-mediated bile acid transport and is itself co-transported with a stoichiometry of 2:1 (GSH:bile acid); this cotransport was not observed for OATP1B1, suggesting OATP1B3 may function as a bidirectional transporter acting as a basolateral organic anion export route. Xenopus oocyte expression system with cholic acid methyl ester loading; radiolabeled trans-activation/inhibition assays; kinetic analysis The Journal of biological chemistry Medium 16877380
2007 Bosentan and its metabolite Ro 48-5033 are substrates of OATP1B3; cyclosporin A and rifampicin inhibit OATP1B3-mediated bosentan uptake with IC50 values below effective plasma concentrations; sildenafil also inhibits OATP1B3-mediated transport at supratherapeutic concentrations, establishing inhibition of hepatic uptake as the mechanism of drug-drug interactions. CHO cells stably expressing OATP1B1 and OATP1B3; radiolabeled uptake assay; IC50 determination; comparison with clinical plasma concentrations Drug metabolism and disposition Medium 17496208
2007 OATP1B3 is the only human OATP capable of transporting paclitaxel to a significant extent among OATP1A2, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, and NTCP tested; common SNPs 334T>G and 699G>A in SLCO1B3 were not associated with paclitaxel pharmacokinetics in European patients. Xenopus laevis oocyte cRNA injection; radiolabeled [3H]paclitaxel accumulation assay; clinical pharmacokinetic study with SNP genotyping Clinical pharmacology and therapeutics Medium 17186002
2007 Microcystin-LR is actively transported into cells via OATP1B3 (Km ~1.2 µM); OATP1B3-mediated uptake results in PP2A inhibition and apoptosis through activation of multiple MAPK pathways (ERK1/2, JNK, p38); cytotoxicity is blocked by MAPK inhibitors (U0126, SP600125, SB203580) and by OATP1B3 substrates/inhibitors. HEK293 cells stably expressing OATP1B3; radiolabeled microcystin-LR uptake assay; FACS apoptosis analysis; phosphatase activity assay; MAPK inhibitor studies Toxicological sciences Medium 17369605
2008 OATP1B3 transports testosterone in a saturable, active manner; cells transfected with SLCO1B3 wild-type (334T/699G) transport testosterone, whereas the double-variant haplotype (334G/699A) impairs testosterone uptake, establishing a substrate-specific effect of this common haplotype. Cos-7 cell transfection with wild-type and variant SLCO1B3 constructs; testosterone transport assay; fluorescence microscopy for tissue expression Clinical cancer research Medium 18519758
2008 OATP1B3 overexpression in colorectal cancer cells with wild-type p53 confers resistance to camptothecin- and oxaliplatin-induced apoptosis; this effect is dependent on transport activity (transport-dead G583E mutant lacks the antiapoptotic effect); OATP1B3 reduces p53 transcriptional activity and downstream targets p21WAF1 and PUMA. Stable overexpression in colorectal cancer cell lines (RKO, HCT-8, HCT116 p53+/+, p53-/-); cytotoxicity assay; TUNEL assay; p53 transcriptional activity reporter; RT-PCR and immunoblot for p53 targets; transport-dead G583E mutant control Cancer research Medium 19074900
2012 Complete simultaneous deficiency of OATP1B1 and OATP1B3 causes Rotor syndrome; OATP1B3 mediates hepatic reuptake of bilirubin conjugates secreted into blood by MRP3/ABCC3; transgenic expression of human OATP1B3 alone in Oatp1a/1b-deficient mice restores bilirubin conjugate clearance, confirming its independent sufficiency as a hepatic reuptake transporter. Genetic analysis of Rotor syndrome families (mutation identification); Oatp1a/1b knockout mice; Abcc3-knockout mice; OATP1B3-transgenic rescue experiments; plasma bilirubin measurement The Journal of clinical investigation High 22232210
2012 Three discrete structural regions of OATP1B3—transmembrane helices 1 and 10, and extracellular loop 6—determine substrate specificity for CCK-8; point mutations at three key residues in the corresponding positions of OATP1B1 confer gain-of-function CCK-8 transport without affecting atorvastatin or estrone sulfate transport. Homologous recombination-based chimeric transporter library in E. coli; site-directed mutagenesis; functional transport assays in transfected cells Molecular pharmaceutics High 22352740
2012 The cancer-specific OATP1B3 variant (V1/Ct-OATP1B3), which lacks the first 28 N-terminal amino acids compared to liver-type OATP1B3, localizes predominantly to the cytoplasm rather than the plasma membrane and shows only modest CCK-8 transport activity compared to wild-type OATP1B3; the variant undergoes different post-translational modifications and increased proteasomal degradation. RT-PCR identification of variant; exogenous expression in HEK293T cells; subcellular fractionation and immunoblotting; transport assay for CCK-8; proteasome inhibitor treatment Molecular pharmaceutics Medium 23215050
2013 Wnt/β-catenin signalling activates OATP1B3 expression in HCC; LiCl treatment (Wnt activator) induced OATP1B3 mRNA in KYN-2 HCC cells; OATP1B3 expression correlates significantly with Wnt/β-catenin target gene expression in HCC clinical samples; OATP1B3 is the primary transporter mediating gadoxetic acid (Gd-EOB-DTPA) uptake in HCC. LiCl Wnt-pathway activation in KYN-2 cells; qRT-PCR and immunohistochemistry of clinical HCC samples; comprehensive transporter mRNA profiling; correlation analysis with Wnt target genes and EOB-MRI enhancement Journal of hepatology Medium 24946283
2013 Sorafenib-glucuronide is a substrate of OATP1B3 (6.4-fold uptake vs. control) and OATP1B1; plasma levels of sorafenib-glucuronide were increased >8-fold in Oatp1b2-knockout mice; expression of human OATP1B3 in knockout mice partially restored normal sorafenib-glucuronide pharmacokinetics. HEK293 cells stably expressing OATP1B3 or OATP1B1; Oatp1b2-knockout mice; OATP1B3-transgenic rescue mice; pharmacokinetic analysis; hepatic/intestinal microsome metabolism assay Clinical cancer research Medium 23340295
2013 Hypoxia inducible factor-1α (HIF-1α) drives transcription of cancer-specific OATP1B3 (csOATP1B3) via two functional hypoxia response elements (HREs) identified by reporter assays and EMSA; siRNA knockdown of HIF-1α substantially decreases csOATP1B3 expression; wild-type liver OATP1B3 is not induced by hypoxia. Luciferase reporter assays with deletion/mutated csOATP1B3 promoter constructs; EMSA with biotin-labeled HRE probe; siRNA knockdown; RT-PCR and immunoblotting; chromatin immunoprecipitation (CIP assay referenced in related study) Biochemical pharmacology Medium 23924606
2014 PKC activation (via PMA) rapidly decreases OATP1B3 transport activity without affecting total protein or mRNA levels or surface expression; the mechanism involves increased phosphorylation of OATP1B3 at Ser/Thr/Tyr residues; PKC inhibitor BIM I blocks PMA-induced inhibition, confirming PKC mediates the post-translational regulation. Human sandwich-cultured hepatocytes; adenoviral FLAG-Myc-tagged OATP1B3 transduction; surface biotinylation; anti-phospho-Ser/Thr/Tyr immunoprecipitation; radiolabeled CCK-8 accumulation assay; PKC inhibitor pretreatment Drug metabolism and disposition High 25200870
2014 OATP1B3 is expressed in pancreatic β-islet cells; glibenclamide is a substrate of OATP1B3; OATP1B3 overexpression in MIN6 murine β-cells enhances the insulinotropic effect of glibenclamide without affecting glucose-stimulated insulin secretion, establishing OATP1B3 as a determinant of glibenclamide efficacy at the tissue level. MDCKII cell transport assay; CCK-8 uptake inhibition assay; transient OATP1B3 overexpression in MIN6 cells; glucose-stimulated and glibenclamide-stimulated insulin secretion assay Diabetes Medium 24150606
2016 Loss of SLCO1B3 expression in prostate cancer drives taxane resistance; silencing SLCO1B3 in chemo-naive PC346C cells decreased intracellular docetaxel and cabazitaxel concentrations ~2-fold; SLCO1B3 overexpression increased sensitivity to both taxanes; SLCO1B3 was significantly downregulated in docetaxel-resistant patient-derived xenografts with decreased intratumoural drug concentrations. Patient-derived xenograft models; next-generation sequencing; siRNA knockdown; SLCO1B3 overexpression; [14C]-docetaxel and [14C]-cabazitaxel uptake assays; cytotoxicity assays British journal of cancer Medium 27537383
2017 The N-terminal region of OATP1B3 (amino acids 12–28) is essential for plasma membrane trafficking; the first 50 N-terminal amino acids are sufficient to drive membrane localization; cancer-type OATP1B3 variant lacking the first 28 amino acids is cytoplasmic, consistent with the N-terminal requirement; this property is shared with OATP1B1 and rat Oatp1b2. N-terminal truncation and point mutants expressed in HEK293T, HCT-8, and MDCK II cells; subcellular fractionation and immunoblotting; N-terminal fusion constructs Biochemical pharmacology Medium 28216016
2017 OATP1B3 mediates testosterone influx with Km = 23.2 µmol/L and Vmax = 321.6 pmol/mg/min; in vivo, Slco1b2-/-/hSLCO1B3 knock-in mice have greater hepatic testosterone uptake and lower plasma testosterone exposure than Slco1b2-/- mice; SLCO1B3 is the second-most differentially expressed transporter in CRPC vs. androgen-sensitive cells (116-fold). Doxycycline-inducible SLCO1B3 cell system; [3H]-testosterone uptake with kinetic analysis; Slco1b2-/- and hSLCO1B3 knock-in mouse pharmacokinetic studies; siRNA knockdown in CRPC cells Molecular cancer research High 28389619
2020 OATP1B3 forms hetero-oligomers with OCT1, OATP1B1, and NTCP; co-expression with OCT1 decreases OATP1B3 plasma membrane expression but increases apparent CCK-8 turnover rate; co-expression with OATP1B1 or NTCP increases membrane expression but decreases turnover rate; OCT1 knockdown in human hepatocytes increases OATP1B3 function. Co-immunoprecipitation from human hepatocytes; proximity ligation assay in HEK293 cells and human liver sections; surface biotinylation; CCK-8 transport assay; siRNA OCT1 knockdown in human hepatocytes Drug metabolism and disposition Medium 32482756
2021 abiraterone treatment induces SLCO1B3 expression in prostate cancer cells (22Rv1) in vitro and in xenografts in vivo; the mechanism involves abiraterone-mediated downregulation of hsa-miR-579-3p, which normally suppresses SLCO1B3; hsa-miR-579-3p was confirmed to bind the SLCO1B3 3'UTR and inhibit its expression by dual luciferase reporter assay. qPCR in prostate cancer cell lines; NanoString miRNA profiling; TargetScan/miRanda prediction; dual luciferase reporter assay with SLCO1B3 3'UTR; 22Rv1 xenograft model in vivo Scientific reports Medium 34031488
2022 Cancer-type OATP1B3 (Ct-OATP1B3) directly interacts with IGF2BP2 (an RNA-binding protein); this interaction stabilizes CPT1A and NDUFA2 mRNAs, increasing their expression and thereby elevating mitochondrial fatty acid β-oxidation and oxidative phosphorylation, which promotes ATP production and lamellipodia formation to drive ovarian cancer cell migration and invasion. Co-immunoprecipitation of Ct-OATP1B3 with IGF2BP2; RNA-binding protein pulldown; mRNA stability assay; seahorse metabolic assay; lamellipodia imaging; in vivo xenograft metastasis model; siRNA knockdown Cell death & disease Medium 35717493

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the hepatic uptake of pitavastatin in humans. The Journal of pharmacology and experimental therapeutics 361 15159445
2009 Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma. Journal of gastroenterology 286 19404564
2012 Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. The Journal of clinical investigation 278 22232210
2007 Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug metabolism and disposition: the biological fate of chemicals 232 17496208
2011 The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging. European radiology 204 21626360
2013 Genetics is a major determinant of expression of the human hepatic uptake transporter OATP1B1, but not of OATP1B3 and OATP2B1. Genome medicine 170 23311897
2008 Effect of SLCO1B3 haplotype on testosterone transport and clinical outcome in caucasian patients with androgen-independent prostatic cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 162 18519758
2001 Vectorial transport by double-transfected cells expressing the human uptake transporter SLC21A8 and the apical export pump ABCC2. Molecular pharmacology 159 11641421
2014 The roles of MRP2, MRP3, OATP1B1, and OATP1B3 in conjugated hyperbilirubinemia. Drug metabolism and disposition: the biological fate of chemicals 156 24459177
2004 Mutations in the SLCO1B3 gene affecting the substrate specificity of the hepatocellular uptake transporter OATP1B3 (OATP8). Pharmacogenetics 149 15226676
2011 SLCO2B1 and SLCO1B3 may determine time to progression for patients receiving androgen deprivation therapy for prostate cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 148 21606417
2006 Predominant contribution of OATP1B3 to the hepatic uptake of telmisartan, an angiotensin II receptor antagonist, in humans. Drug metabolism and disposition: the biological fate of chemicals 144 16611857
2008 Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. European journal of pharmacology 143 18321482
2013 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clinical cancer research : an official journal of the American Association for Cancer Research 142 23340295
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
2014 OATP1B3 expression is strongly associated with Wnt/β-catenin signalling and represents the transporter of gadoxetic acid in hepatocellular carcinoma. Journal of hepatology 132 24946283
2007 Potent cytotoxicity of the phosphatase inhibitor microcystin LR and microcystin analogues in OATP1B1- and OATP1B3-expressing HeLa cells. Molecular cancer therapeutics 127 17308056
2007 Variants in the SLCO1B3 gene: interethnic distribution and association with paclitaxel pharmacokinetics. Clinical pharmacology and therapeutics 123 17186002
2011 Expression of SLCO transport genes in castration-resistant prostate cancer and impact of genetic variation in SLCO1B3 and SLCO2B1 on prostate cancer outcomes. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 120 21266523
2007 Involvement of mitogen-activated protein kinase signaling pathways in microcystin-LR-induced apoptosis after its selective uptake mediated by OATP1B1 and OATP1B3. Toxicological sciences : an official journal of the Society of Toxicology 120 17369605
2008 Overexpression of OATP1B3 confers apoptotic resistance in colon cancer. Cancer research 117 19074900
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 113 23243220
2009 Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia. Human molecular genetics 113 19419973
2013 An EAV-HP insertion in 5' Flanking region of SLCO1B3 causes blue eggshell in the chicken. PLoS genetics 104 23359636
2003 Detection of the human organic anion transporters SLC21A6 (OATP2) and SLC21A8 (OATP8) in liver and hepatocellular carcinoma. Laboratory investigation; a journal of technical methods and pathology 102 12695556
2004 The human organic anion transporting polypeptide 8 (SLCO1B3) gene is transcriptionally repressed by hepatocyte nuclear factor 3beta in hepatocellular carcinoma. Journal of hepatology 93 14739090
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 83 29538325
2006 OATP1B1, OATP1B3, and mrp2 are involved in hepatobiliary transport of olmesartan, a novel angiotensin II blocker. Drug metabolism and disposition: the biological fate of chemicals 82 16501004
2015 Inhibitory Effects of Green Tea and (-)-Epigallocatechin Gallate on Transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-Glycoprotein. PloS one 74 26426900
2012 A cancer-specific variant of the SLCO1B3 gene encodes a novel human organic anion transporting polypeptide 1B3 (OATP1B3) localized mainly in the cytoplasm of colon and pancreatic cancer cells. Molecular pharmaceutics 73 23215050
2006 Vectorial transport of enalapril by Oatp1a1/Mrp2 and OATP1B1 and OATP1B3/MRP2 in rat and human livers. The Journal of pharmacology and experimental therapeutics 71 16627748
2012 Long-lasting inhibitory effects of cyclosporin A, but not tacrolimus, on OATP1B1- and OATP1B3-mediated uptake. Drug metabolism and pharmacokinetics 70 22240838
2011 Sodium fluorescein is a probe substrate for hepatic drug transport mediated by OATP1B1 and OATP1B3. Journal of pharmaceutical sciences 69 21837650
2018 PBPK Modeling of Coproporphyrin I as an Endogenous Biomarker for Drug Interactions Involving Inhibition of Hepatic OATP1B1 and OATP1B3. CPT: pharmacometrics & systems pharmacology 66 30175555
2006 OATP8/1B3-mediated cotransport of bile acids and glutathione: an export pathway for organic anions from hepatocytes? The Journal of biological chemistry 66 16877380
2007 Rapid screening of antineoplastic candidates for the human organic anion transporter OATP1B3 substrates using fluorescent probes. Cancer letters 64 18082941
2015 OATP1B1 and tumour OATP1B3 modulate exposure, toxicity, and survival after irinotecan-based chemotherapy. British journal of cancer 61 25611302
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 60 16686371
2011 The effects of CYP3A4, CYP3A5, ABCB1, ABCC2, ABCG2 and SLCO1B3 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of docetaxel in nasopharyngeal carcinoma patients. Cancer chemotherapy and pharmacology 58 21468756
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
2014 Selectivity and potency of microcystin congeners against OATP1B1 and OATP1B3 expressing cancer cells. PloS one 57 24614281
2016 Loss of SLCO1B3 drives taxane resistance in prostate cancer. British journal of cancer 55 27537383
2015 Molecular mechanisms governing different pharmacokinetics of ginsenosides and potential for ginsenoside-perpetrated herb-drug interactions on OATP1B3. British journal of pharmacology 54 25297453
2005 Vectorial transport of the peptide CCK-8 by double-transfected MDCKII cells stably expressing the organic anion transporter OATP1B3 (OATP8) and the export pump ABCC2. The Journal of pharmacology and experimental therapeutics 53 15665139
2014 Human OATP1B1, OATP1B3 and OATP1A2 can mediate the in vivo uptake and clearance of docetaxel. International journal of cancer 50 24825069
2012 Beta-catenin-activated hepatocellular adenoma showing hyperintensity on hepatobiliary-phase gadoxetic-enhanced magnetic resonance imaging and overexpression of OATP8. Japanese journal of radiology 49 22911100
2008 Permeation of Boswellia extract in the Caco-2 model and possible interactions of its constituents KBA and AKBA with OATP1B3 and MRP2. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 45 19010411
2016 The Nonmetabolized β-Blocker Nadolol Is a Substrate of OCT1, OCT2, MATE1, MATE2-K, and P-Glycoprotein, but Not of OATP1B1 and OATP1B3. Molecular pharmaceutics 42 26702643
2014 Novel mechanism of impaired function of organic anion-transporting polypeptide 1B3 in human hepatocytes: post-translational regulation of OATP1B3 by protein kinase C activation. Drug metabolism and disposition: the biological fate of chemicals 42 25200870
2011 Expression of SLCO1B3 is associated with intratumoral cholestasis and CTNNB1 mutations in hepatocellular carcinoma. Cancer science 39 21615622
2017 Pretreatment With Rifampicin and Tyrosine Kinase Inhibitor Dasatinib Potentiates the Inhibitory Effects Toward OATP1B1- and OATP1B3-Mediated Transport. Journal of pharmaceutical sciences 37 28373111
2006 Polymorphisms and linkage disequilibrium of the OATP8 (OATP1B3) gene in Japanese subjects. Drug metabolism and pharmacokinetics 37 16702737
2020 Role of OATP1B1 and OATP1B3 in Drug-Drug Interactions Mediated by Tyrosine Kinase Inhibitors. Pharmaceutics 36 32916864
2014 Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of tyrosine kinase inhibitors. Drug metabolism and drug interactions 36 24643910
2008 Organic anion transporting polypeptide 1B3 (OATP1B3) is overexpressed in colorectal tumors and is a predictor of clinical outcome. Clinical and experimental gastroenterology 35 21677819
2015 Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Molecular pharmaceutics 34 26474710
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 32 29746136
2012 Influence of SLCO1B3 haplotype-tag SNPs on docetaxel disposition in Chinese nasopharyngeal cancer patients. British journal of clinical pharmacology 32 21995462
2011 Alteration in placental expression of bile acids transporters OATP1A2, OATP1B1, OATP1B3 in intrahepatic cholestasis of pregnancy. Archives of gynecology and obstetrics 32 22203093
2011 Development of a multiplex UPLC-MRM MS method for quantification of human membrane transport proteins OATP1B1, OATP1B3 and OATP2B1 in in vitro systems and tissues. Analytica chimica acta 32 22304817
2005 Development of a fluorescence-based assay for screening of modulators of human organic anion transporter 1B3 (OATP1B3). European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 32 16129589
2022 Ct-OATP1B3 promotes high-grade serous ovarian cancer metastasis by regulation of fatty acid beta-oxidation and oxidative phosphorylation. Cell death & disease 31 35717493
2015 Correlation between Gd-EOB-DTPA-enhanced MR imaging findings and OATP1B3 expression in chemotherapy-associated sinusoidal obstruction syndrome. Abdominal imaging 31 26187715
2013 Role of hypoxia inducible factor-1α in the regulation of the cancer-specific variant of organic anion transporting polypeptide 1B3 (OATP1B3), in colon and pancreatic cancer. Biochemical pharmacology 31 23924606
2011 Nostocyclopeptide-M1: a potent, nontoxic inhibitor of the hepatocyte drug transporters OATP1B3 and OATP1B1. Molecular pharmaceutics 31 21214185
2014 Preserved or enhanced OATP1B3 expression in hepatocellular adenoma subtypes with nuclear accumulation of β-catenin. Hepatology research : the official journal of the Japan Society of Hepatology 30 25418671
2014 Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors. Drug metabolism and drug interactions 29 24807167
2021 SLCO1B3 promotes colorectal cancer tumorigenesis and metastasis through STAT3. Aging 28 34526411
2011 Influence of genomic ancestry on the distribution of SLCO1B1, SLCO1B3 and ABCB1 gene polymorphisms among Brazilians. Basic & clinical pharmacology & toxicology 26 22136368
2008 Influence of SLCO1B3 gene polymorphism on the pharmacokinetics of digoxin in terminal renal failure. Drug metabolism and pharmacokinetics 25 19122334
2019 Preincubation With Everolimus and Sirolimus Reduces Organic Anion-Transporting Polypeptide (OATP)1B1- and 1B3-Mediated Transport Independently of mTOR Kinase Inhibition: Implication in Assessing OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions. Journal of pharmaceutical sciences 24 31047942
2013 OATP1B3 is expressed in pancreatic β-islet cells and enhances the insulinotropic effect of the sulfonylurea derivative glibenclamide. Diabetes 24 24150606
2012 Influence of SLCO1B3 genetic variations on tacrolimus pharmacokinetics in renal transplant recipients. Drug metabolism and pharmacokinetics 22 23149872
2019 Impact of SLCO1B3 polymorphisms on clinical outcomes in lung allograft recipients receiving mycophenolic acid. The pharmacogenomics journal 21 30992538
2017 Aberrant expression of OATP1B3 in colorectal cancer liver metastases and its clinical implication on gadoxetic acid-enhanced MRI. Oncotarget 21 29050339
2013 Do SLCO1B3 (T334G) and CYP3A5*3 polymorphisms affect response in Egyptian chronic myeloid leukemia patients receiving imatinib therapy? Hematology (Amsterdam, Netherlands) 21 23394475
2012 Organic anion transporting polypeptides OATP1B1 and OATP1B3 and their genetic variants influence the pharmacokinetics and pharmacodynamics of raloxifene. Journal of translational medicine 21 22533838
2013 Type VII collagen regulates expression of OATP1B3, promotes front-to-rear polarity and increases structural organisation in 3D spheroid cultures of RDEB tumour keratinocytes. Journal of cell science 20 24357722
2012 Interaction of three regiospecific amino acid residues is required for OATP1B1 gain of OATP1B3 substrate specificity. Molecular pharmaceutics 19 22352740
2020 The Emerging Role of the SLCO1B3 Protein in Cancer Resistance. Protein and peptide letters 18 31556849
2017 Differential Expression of OATP1B3 Mediates Unconjugated Testosterone Influx. Molecular cancer research : MCR 18 28389619
2015 Naringin attenuates the cytotoxicity of hepatotoxin microcystin-LR by the curious mechanisms to OATP1B1- and OATP1B3-expressing cells. Environmental toxicology and pharmacology 18 25818985
2015 Microcystin LR Shows Cytotoxic Activity Against Pancreatic Cancer Cells Expressing the Membrane OATP1B1 and OATP1B3 Transporters. Anticancer research 18 26504008
2013 An in vivo hypoxia metagene identifies the novel hypoxia inducible factor target gene SLCO1B3. European journal of cancer (Oxford, England : 1990) 18 23352438
2018 Cancer-Type OATP1B3 mRNA in Extracellular Vesicles as a Promising Candidate for a Serum-Based Colorectal Cancer Biomarker. Biological & pharmaceutical bulletin 16 29491222
2017 The N-terminal region of organic anion transporting polypeptide 1B3 (OATP1B3) plays an essential role in regulating its plasma membrane trafficking. Biochemical pharmacology 16 28216016
2020 OATP1B3 Expression and Function is Modulated by Coexpression with OCT1, OATP1B1, and NTCP. Drug metabolism and disposition: the biological fate of chemicals 15 32482756
2019 Association Between the Methylation Statuses at CpG Sites in the Promoter Region of the SLCO1B3, RNA Expression and Color Change in Blue Eggshells in Lushi Chickens. Frontiers in genetics 15 30863430
2015 Generation of Bayesian prediction models for OATP-mediated drug-drug interactions based on inhibition screen of OATP1B1, OATP1B1∗15 and OATP1B3. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 15 25603031
2015 Polymorphisms in SLCO1B3 and NR1I2 as genetic determinants of hematotoxicity of carboplatin and paclitaxel combination. Pharmacogenomics 15 26267044
2014 Kinetic Interpretation of the Importance of OATP1B3 and MRP2 in Docetaxel-Induced Hematopoietic Toxicity. CPT: pharmacometrics & systems pharmacology 15 25054314
2011 Functional consequences of genetic variations in the human organic anion transporting polypeptide 1B3 (OATP1B3) in the Korean population. Journal of pharmaceutical sciences 15 22147445
2010 Organic anion transporting polypeptide 1B1 (OATP1B1) and OATP1B3: genetic variability and haplotype analysis in white Canadians. Drug metabolism and pharmacokinetics 15 20877131
2021 Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p. Scientific reports 14 34031488
2020 Effect of Rifampin-Mediated OATP1B1 and OATP1B3 Transporter Inhibition on the Pharmacokinetics of the P2Y12 Receptor Antagonist Selatogrel. Clinical and translational science 14 32166864
2015 Okadaic acid is taken-up into the cells mediated by human hepatocytes transporter OATP1B3. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 14 26134461
2020 Association of the Trough, Peak/Trough Ratio of Imatinib, Pyridine-N-Oxide Imatinib and ABCG2 SNPs 34 G>A and SLCO1B3 334 T>G With Imatinib Response in Egyptian Chronic Myeloid Leukemia Patients. Frontiers in oncology 13 32974132
2017 Interactions of crizotinib and gefitinib with organic anion-transporting polypeptides (OATP)1B1, OATP1B3 and OATP2B1: gefitinib shows contradictory interaction with OATP1B3. Xenobiotica; the fate of foreign compounds in biological systems 13 28005438
2023 Relevance of the organic anion transporting polypeptide 1B3 (OATP1B3) in the personalized pharmacological treatment of hepatocellular carcinoma. Biochemical pharmacology 12 37429423
2017 Characterization of OATP1B3 and OATP2B1 transporter expression in the islet of the adult human pancreas. Histochemistry and cell biology 12 28493059

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