Ask about this productRelated genes to: SLCO2B1 Blocking Peptide
- Gene:
- SLCO2B1 NIH gene
- Name:
- solute carrier organic anion transporter family member 2B1
- Previous symbol:
- SLC21A9
- Synonyms:
- OATP-B, OATP2B1
- Chromosome:
- 11q13
- Locus Type:
- gene with protein product
- Date approved:
- 2000-02-01
- Date modifiied:
- 2015-11-18
Related products to: SLCO2B1 Blocking Peptide
Related articles to: SLCO2B1 Blocking Peptide
- Pentamidine is an FDA-approved antiparasitic drug used to treat African trypanosomiasis caused by Trypanosoma brucei, as well as Pneumocystis and Leishmania infections, however, its clinical utility is limited by poor blood-brain barrier penetration and severe side effects. In human cells, pentamidine uptake is primarily mediated by the organic cation transporter OCT1 and the organic anion-transporting polypeptide OATP1A2, while efflux occurs via the multidrug transporter P-glycoprotein (ABCB1). Here, we present a comprehensive experimental and computational characterization of six pentamidine analogs and their interactions with OATP1A2, OATP2B1, and ABCB1. Fluorescence-based uptake assays revealed that all analogs potently inhibit OATP1A2, with three compounds (4 - 6) exceeding the inhibitory potency of pentamidine. In contrast, inhibition of OATP2B1 was weaker and compound-specific, demonstrating clear transporter selectivity. Cell viability assays identified all analogs as OATP1A2 substrates, whereas in accordance with the uptake assay results, viability of OATP2B1-expressing cells was not altered by any of the tested compounds. Mechanistic studies confirmed apoptosis as the primary mode of cell death. ABCB1 overexpression substantially reduced cytotoxicity, highlighting a critical interplay between uptake and efflux transporters, and also indicating that function of ABCB1 may limit bioavailability of the compounds. Molecular docking and molecular dynamics simulations revealed that steric bulk and conformational rigidity of amidino substituents - most prominently in the N,N'-cyclohexylamidino derivative - underpin high-affinity OATP1A2 binding, while all compounds were accommodated within the ABCB1 substrate-binding cavity, consistent with efflux activity. Collectively, this study identifies OATP1A2 as a key determinant of pentamidine analog uptake and highlights the importance of transporter interplay in shaping intracellular drug exposure and pharmacological response. - Source: PubMed
Publication date: 2026/04/18
Fülöp SáraBakos ÉvaKaźmierczak PawełSzalai OrsolyaŚpiołek MariaYazdi Zeinab NezafatUngvári OrsolyaŻołek TeresaÖzvegy-Laczka Csilla - Macrophages are important hosts for intracellular pathogens. Drug transporters modulate the uptake and thus efficacy of antibiotics in macrophages. However, there is only few data comparing drug transporter expression levels in polarized pro-inflammatory M1 to anti-inflammatory M2 macrophages. THP-1 monocytes were differentiated with 200 nM phorbol 12-myristate 13-acetate for 72 h and subsequently polarized to the M1 (50 ng/mL lipopolysaccharide, 20 ng/mL interferon-gamma; 48 h) or the M2 (20 ng/mL interleukin-4, interleukin-13; 48 h) phenotype. Using a quantitative polymerase-chain reaction array, mRNA levels of 84 drug transporters were evaluated. Western blotting was used to assess P-glycoprotein (P-gp, encoded by ABCB1) protein expression. Finally, expression of 46 P-gp-regulating microRNA species was evaluated as well. Compared to M2 macrophages, seven transporter genes were lower expressed in M1 cells (e.g., ABCG2 threefold; SLCO2B1 7.5-fold) and 21 genes were higher expressed. ABCB1 mRNA was in fact up-regulated threefold, but 2.4-fold lower at the protein level. This discrepancy associated with a 5.5-fold higher expression of miR-21-3p and a 128-fold lower expression of miR-145-3p. In conclusion, M1 and M2 macrophages differ by drug transporter transcriptomics. The discrepancy of ABCB1 mRNA and P-gp protein levels in M1 macrophages associates with the high abundance of miR-21-3p, a regulator of "RNA binding protein, mRNA processing factor." - Source: PubMed
Publication date: 2026/04/11
Hamburg KatharinaWeiss JohannaStingl Julia CarolinTheile Dirk - Organic anion transporting polypeptides (OATP)1B1/1B3 are mainly expressed in the liver, whereas OATP2B1 is expressed in the liver as well as in the intestine. Coproporphyrin (CP)-I has been reported to be a highly sensitive biomarker for the OATP family, and its isomer, CP-III, is transported not only by OATP1B1 but also by OATP2B1. Thus, hepatic OATP1B1/1B3 and OATP2B1 activities may be predicted by measuring CP-I and CP-III. We measured plasma CP-I and CP-III concentrations in a sample of Japanese general population and evaluated the relationship between the CP isomers and polymorphisms in the OATP family. In addition, we evaluated the performance of CP-I, CP-III, and CP-I+CP-III (assuming that CP-I and CP-III are not separated) using receiver operating characteristic curves. Plasma CP-I concentration was significantly higher in OATP1B1∗15 carriers (participants with polymorphisms that reduce OATP1B1 activity) than in wild-type OATP1B1 participants (P < .05 for all). Although there was a slight difference in plasma CP-I concentration in OATP2B1 polymorphism, there were no differences in plasma CP-I and CP-III concentrations between groups based on OATP2B1 and OATP1B3 polymorphisms. Also, the area under the receiver operating characteristic curve of CP-I for discriminating OATP1B1∗15 carriers was significantly larger than those of CP-III and CP-I+CP-III (P < .05). In conclusion, plasma CP-III concentration is unsuitable as a hepatic OATP2B1 biomarker. On the other hand, CP-I is a highly sensitive endogenous biomarker for the assessment of OATP1B1 activity, and quantification of CP-I separated from CP-III is desirable for more accurate prediction of OATP1B1 activity. SIGNIFICANCE STATEMENT: Coproporphyrin (CP)-I and CP-III were spotlighted as endogenous biomarkers for evaluating hepatic organic anion transporting polypeptide (OATP) activity. This study evaluates the relationship between the CP isomers and polymorphisms in the OATP family and the performance of CP-I, CP-III, and CP-I+CP-III as an OATP1B1 biomarker. The results indicate that CP-III is unsuitable as a biomarker for the OATP family, while reinforcing the evidence of CP-I as a specific OATP1B1 biomarker, and contributes to more specific evaluation of OATP1B1 activity. - Source: PubMed
Publication date: 2026/03/17
Negami JunSuzuki YosukeKoyama TeruhideYamazaki MiharuOda AyakoOzaki EtsukoYamamoto YasuyukiNakatochi MasahiroMomozawa YukihideTakashima NaoyukiMatsuo KeitaroOhno Keiko - Human prenatal exposure to bisphenol analogues (BPs) and their conjugated BP metabolites may pose risks to fetal development. However, studies comprehensively investigating the transplacental transfer of BPs and their conjugated metabolites remain limited. This study provides the most comprehensive investigation on presence, transplacental transfer efficiencies, and potential influence of placental transporters for 12 BPs and 14 conjugated BP metabolites in maternal and cord plasma samples (147 pairs) from Chinese participants. Bisphenol A (BPA) and bisphenol SIP (BPSIP) were consistently detected as the most abundant BPs in maternal (mean 0.98 ng/mL and 0.59 ng/mL, respectively) and cord plasma (mean 0.92 ng/mL and 0.66 ng/mL, respectively). BPA-glucuronide (BPA-G) and bisphenol AF-sulfate (BPAF-S) were the predominant conjugated BP metabolites identified in maternal (mean 0.71 ng/mL and 0.66 ng/mL, respectively) and cord plasma (mean 0.71 ng/mL and 0.73 ng/mL, respectively) samples. Among BPs, BPAP (mean 1.2) showed the highest mean transplacental transfer efficiency (TTE) value, followed by BPSIP (1.1), bisphenol F (1.1), and BPA (0.94). Among conjugated BP metabolites, BPAF-G (mean 1.7) exhibited the highest mean TTE, which was followed by BPS-G (1.2) and BPA-G (1.1). Transcript levels of placental transporters ABCA1 and ABCB1 were negatively (p < 0.05) correlated with the TTE of bisphenol M. The transcript levels of solute carrier SLCO2B1 and SLC22A4 were positively (p < 0.05) correlated with the TTE of BPAP. This study advances our understanding of the knowledge on the transplacental transfer behaviors for BPs and their conjugated metabolites, while elucidating the roles of transplacental transporters in modulating fetal exposure. - Source: PubMed
Publication date: 2026/03/30
Li JunxuChen ShengqunWu PengfeiLi Yang - The eukaryotic 5' untranslated region (5' UTR) canonically influences mRNA translation efficiency. Accumulating evidence has demonstrated that alternative promoters generate distinct transcription start sites (TSSs), producing many mRNA isoforms with divergent 5' UTR sequences. Herein, we comprehensively analyzed the 5' UTR sequence structure and protein abundance of RNA transcripts with altered TSSs in hepatocellular carcinoma (HCC). The analysis uncovered an mRNA isoform of solute carrier organic anion transporter family member 2B1 (SLCO2B1), named SLCO2B1-isoformNovel (SLCO2B1-isoN), that was highly expressed in HCC and correlated with poor patient prognosis but did not encode a detectable protein product. The 5' end stem‒loop of SLCO2B1-isoN abrogated its translational capacity and turned it into a noncoding RNA. The SLCO2B1-isoN noncoding isoform stabilized fragile X messenger ribonucleoprotein 1 (FMR1) to trigger HCC progression by facilitating de novo protein biosynthesis. Targeting SLCO2B1-isoN effectively inhibited orthotopic tumor xenograft growth and metastasis in vivo. In conclusion, this study revealed a noncoding isoform of SLCO2B1 mRNA and highlighted the dual characteristics of mRNAs harboring protein-coding and noncoding isoforms. - Source: PubMed
Publication date: 2026/03/26
Qiu WenyingZeng YuFan ZhichaoSu YueJiang JiawenShi QiliLi XinrongLi ShengliSong JunjiaoHe Xianghuo