SLC47A2 antibody
- Known as:
- SLC47A2 (anti-)
- Catalog number:
- orb125139
- Product Quantity:
- 100 ug
- Category:
- -
- Supplier:
- Biorb
- Gene target:
- SLC47A2 antibody
Related genes to: SLC47A2 antibody
- Gene:
- SLC47A2 NIH gene
- Name:
- solute carrier family 47 member 2
- Previous symbol:
- -
- Synonyms:
- FLJ31196, MATE2, MATE2-K
- Chromosome:
- 17p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 2007-05-18
- Date modifiied:
- 2016-02-17
Related products to: SLC47A2 antibody
Related articles to: SLC47A2 antibody
- Abemaciclib increases serum creatinine by inhibiting renal tubular transporters rather than reducing true glomerular filtration rate, a phenomenon known as pseudo-acute kidney injury. Creatinine-cystatin C discrepancy and genetic determinants of this elevation remain insufficiently characterized in Japanese patients. This single-center prospective observational study included 63 Japanese patients with breast cancer receiving abemaciclib. On-treatment serum creatinine and cystatin C were measured in all patients, with pre-treatment cystatin C available in 29. eGFR was calculated using the Japanese equations (eGFRcre, eGFRcys), and the discrepancy quantified as their difference and ratio. Associations between change in serum creatinine and renal transporter polymorphisms (SLC22A2 rs316019, SLC47A1 rs2289669, and SLC47A2 rs12943590) were evaluated by hierarchical regression. Serum creatinine increased in 62 patients (median change, 0.21 mg/dL) and eGFRcre decreased by a median of 20.5 mL/min/1.73 m, whereas on-treatment eGFRcys exceeded eGFRcre by a median of 54.9 mL/min/1.73 m (median ratio 2.07). Relative to baseline, the elevation was CTCAE grade 1 in 57 patients (90.5%) and grade 2 in 5 (7.9%), remained stable through week 24, and fell after drug interruption (0.87 to 0.71 mg/dL, P < 0.001). In the 29-patient sub-cohort the discrepancy widened approximately three-fold, with opposite directional changes in 28 patients. The pre-treatment serum creatinine/cystatin C ratio predicted the on-treatment discrepancy, and SLC47A1 rs2289669 GG was associated with a greater rise, consistent with a MATE1-mediated mechanism. Because a fixed cross-sectional threshold does not separate treatment-associated discrepancy from pre-existing discrepancy, a pre-treatment cystatin C measurement is needed to interpret serum creatinine elevation during abemaciclib therapy. - Source: PubMed
Publication date: 2026/09/22
Watanabe HiroakiHirai KeitaOba TakaakiOno MayuIto Ken-IchiNaito Takafumi - Metformin is a widely used drug with a relatively good efficacy in diabetes treatment, a good safety profile, and the potential for use in other indications. The variability in the individual responses to metformin therapy is partially determined by genetic factors. This narrative review aimed to summarize information on single nucleotide variant (SNVs) in genes for transporter proteins associated with metformin pharmacokinetics and pharmacodynamics and/or the occurrence of adverse effects. The Pharmacogenomics Knowledge Base (PharmGKB) and Web of Science databases were searched for metformin-associated gene variants that could affect its action. Seven transporter genes with twelve SNVs common in the European population were identified in the PharmGKB database, namely SNVs in genes (OCT1), (OCT2), (OCT3), (OCTN1), (MATE1), (MATE2-K) and (GLUT2); it is worth noting that GLUT2 is not metformin transported but a glucose transporter and as such, it can also influence metformin action. Based on 63 retrieved studies, the association of individual SNVs with metformin effectiveness and adverse effects is discussed. In view of the high variability of study designs, populations, and reporting patterns, we also propose a framework for the design and reporting of metformin-associated pharmacogenetic studies, suggesting also that determining a complete set of these SNVs could help in comprehensive understanding of genetically conditioned individual responsiveness to metformin therapy, thus opening the path to maximizing the utilization of its positive effects while minimizing the risk of adverse effects. In addition, given the large variability in designs among studies, we also propose a framework for future studies on SNVs in metformin action-associated transporters that could improve comparability of future studies. - Source: PubMed
Publication date: 2026/06/19
Mlcuchova NatalieLipovy BretislavZendulka OndrejJanosek JaroslavBorilova Linhartova Petra - Regulatory agencies request the assessment of the potential of new drugs to cause transporter-mediated drug-drug interactions (DDI). This assessment can be improved by integrating endogenous biomarkers during drug development. Regarding the renal excretion of drugs such as metformin, the organic cation transporter (OCT) 2 and multidrug and toxin extrusion proteins (MATE) 1 and 2-K are of major importance. However, fully validated, sensitive, and specific biomarkers for these transporters are still lacking. In previous in vivo and in vitro studies, 5-aminovaleric acid betaine (5AVAB), serotonin (5HT), and 1-methylhistamine (1MH) emerged as promising biomarker candidates for OCT2/MATE-mediated DDI. Therefore, we further investigated their suitability for clinical risk assessment by evaluating the effects of the OCT2/MATE inhibitor trimethoprim in healthy volunteers and by determining IC values for the inhibition of OCT2- and/or MATE1-mediated uptake of the potential biomarkers by trimethoprim, cimetidine, pyrimethamine, and dolutegravir in vitro. Trimethoprim reduced the amount excreted into urine of 5AVAB, 5HT, and 1MH in vivo by 95.1 ± 5.67%, 78.9 ± 6.56%, and 51.9 ± 14.3%, respectively (all P < 0.001) as well as the renal clearance of 5AVAB and 5HT by 93.6 ± 5.85% and 73.8 ± 12.8%, respectively (both P < 0.001). When comparing the IC values with unbound inhibitor plasma concentrations, trimethoprim, cimetidine, and pyrimethamine preferentially inhibit the MATE1-mediated transport, whereas dolutegravir inhibits the OCT2-mediated transport of the biomarker candidates. In conclusion, this study further supports the suitability of 5-aminovaleric acid betaine (5AVAB), serotonin (5HT), and 1-methylhistamine (1MH) as promising biomarkers for OCT2/MATE-mediated DDI. - Source: PubMed
Publication date: 2026/07/04
Picurová JanaMüller FabianAuge DanielKönig JörgFromm Martin FGessner Arne - Doravirine (DOR), a potent nonnucleoside reverse transcriptase inhibitor for HIV-1 treatment, is primarily metabolized by cytochrome P450 3A enzymes to form doravirine carboxylic acid metabolite (M9), the major plasma metabolite excreted in urine. To investigate the estimated glomerular filtration rate decrease observed in phase 3 DOR studies, we investigated DOR and M9 interactions with renal transporters organic cation transporter 2 (OCT2), organic anion transporter 2 (OAT2), and multidrug and toxin extrusion proteins 1 and 2K (MATE1 and MATE2K). In vitro assays were conducted in OCT2- and OAT2-transfected human embryonic kidney 293 (HEK293) cells and MATE1- and MATE2K-transfected Madin-Darby canine kidney II cells. The inhibitory potency (half-maximal inhibitory concentration [IC]) of DOR and M9 on OCT2-, OAT2-, MATE1-, and MATE2K-mediated uptake of creatinine or metformin were measured, whereas substrate-dependent inhibition was assessed for OCT2 and MATE1. DOR inhibited OCT2-mediated creatinine uptake with an IC of 6.9 ± 0.8 μM, approximately 6.2-fold lower than that observed using metformin as probe. DOR also inhibited OAT2 at concentrations higher than clinically relevant (IC of 28.7 ± 4.9 μM). DOR did not inhibit MATE1-mediated creatinine uptake (IC >100 μM). M9, at concentrations higher than clinically relevant, inhibited OAT2-mediated creatinine uptake (IC of 18.0 ± 2.1) but did not inhibit creatinine or metformin uptake by OCT2, MATE1, or MATE2K (IC >30 μM for all). In conclusion, at clinically relevant exposures, DOR exhibited substrate-dependent inhibition of creatinine transport via OCT2, which could explain the slight decrease in calculated estimated glomerular filtration rate observed with DOR treatments, without reduction in renal function. SIGNIFICANCE STATEMENT: At clinically relevant concentrations, doravirine inhibits the renal transporter organic cation transporter 2 in a substrate-dependent manner, but not organic anion transporter 2, multidrug and toxin extrusion proteins 1 and 2K, indicating that doravirine-associated estimated glomerular filtration rate reductions are caused by inhibition of renal creatinine transport and do not reflect a reduction in renal function. - Source: PubMed
Publication date: 2026/05/05
Li YangSaran ChitraChu XiaoyanSanchez Rosa IThomas Alana FCarstens Russ PPisculli Mary LKlopfer Stephanie OXu Zhi JinLahoulou RimaPlank Rebeca M - Platinum-based chemotherapeutics remain clinically indispensable for treating various malignancies despite causing severe side effects, with ototoxicity being particularly limiting. This study reports the synthesis and evaluation of platinum(IV) prodrugs incorporating the hearing-protective ligand RG108. Among the synthesized mono- and di-substituted cisplatin and oxaliplatin derivatives, compound 4 exhibited exceptional antitumor activity with an IC value of 0.07 ± 0.08 µM in FaDu cells. Mechanistic investigations revealed that the enhanced anti-tumor effect was primarily mediated via the EZH2/SLC47A2 regulatory axis. These prodrugs significantly mitigated ototoxicity, preserving cochlear hair cell viability, stabilizing auditory brainstem response thresholds, and maintaining cochlear basement membrane morphology. Our findings establish a framework for designing dual-functional platinum agents that synergize antitumor efficacy with organoprotective properties, addressing critical hearing loss limitations of conventional platinum chemotherapy while maintaining robust therapeutic outcomes. - Source: PubMed
Publication date: 2026/03/12
Wu JiyongNie JingWu HuinaWang DongboLi YameiLiang MinyanQian HuimeiWang Yong