SLC47A2 Blocking Peptide, Blocking Peptides
- Known as:
- SLC47A2 Blocking Peptide, Blocking Peptides
- Catalog number:
- 33R-9403
- Product Quantity:
- 100 ug
- Category:
- -
- Supplier:
- Fitzgerald
- Gene target:
- SLC47A2 Blocking Peptide Peptides
Related genes to: SLC47A2 Blocking Peptide, Blocking Peptides
- 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 Blocking Peptide, Blocking Peptides
Related articles to: SLC47A2 Blocking Peptide, Blocking Peptides
- 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 - Diabetes type 2 (DT2) entails significant health, economic, and productivity repercussions around the world. Poor glycaemic control, defined as an HbA1c >7.0%, has been associated with a number of complications. In spite of the large share of healthcare resources allocated to DT2 treatment, the proportion of controlled Mexican patients is among the lowest in the world (34.4%). Certain protein-encoding genetic polymorphisms involved in metformin transport may affect glycaemic control. We focused on determining the frequency of rs2289669, rs2252281, rs12943590, and rs34834489 polymorphisms in Mexican-Mestizo patients from the Tertiary Care Regional Hospital of Ixtapaluca, State of Mexico, Mexico, as well as assessing their possible association with therapeutic efficacy, as estimated through glycated haemoglobin. The individual polymorphism analysis did not reveal an association with glycaemic control; however, when combined with rs72552763 and rs622342, we found a significant positive correlation between HbA1c levels and metformin dose, which prevailed among patients carrying allelic variants of rs2289669 or rs12943590 who were also simultaneously carrying allelic variants of rs72552763 or rs622342. Patients carrying the reference allele of rs34834489 reported a significant positive correlation between HbA1c levels and metformin dose as well, regardless of their rs72552763 or rs622342 genotype. Thus, we identified alleles and allelic combinations of , , and polymorphisms posing a potential glycaemic control risk in Mexican-Mestizo patients. - Source: PubMed
Publication date: 2025/09/05
Gómez-Hernández Milton AbrahamOrtega-Ayala AdielRodríguez-Lima OscarLanda AbrahamAcosta-Altamirano GustavoMolina-Guarneros Juan A - This study explores the relationship between gene polymorphisms and glycemic responses across ethnic populations and identifies optimal therapy combinations for glycemic control. However, the definition of glycemic response varied across included studies (e.g., HbA1c <7 %, or >0.5 % reduction), which may affect the comparability and interpretation of pooled data. - Source: PubMed
Publication date: 2025/06/24
Ahmad FikryAbubakar SuhailiSyed Alwi Sharifah SakinahChuan Ng Ooi - The multidrug and toxin extrusion proteins MATE1 and MATE2K may determine the pharmacokinetics and drug-drug interactions of many drugs. However, their substrate spectrum and synergy with organic cation transporters OCT1 and OCT2 remain incompletely understood. Therefore, we screened 590 predominantly positively charged, low molecular weight compounds for transport via these four transporters in HEK293 cells using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). MATE1 and MATE2K transported 164 and 114 compounds, respectively, with significant overlap. High-affinity substrates included berberine, pentamidine, and amisulpride, while epinephrine and atenolol had the highest . Despite less than 16% sequence homology, there was high overlap among MATE1/-2K and OCT1/-2 substrates. Neither isolated physicochemical properties nor their linear combinations predicted the substrates of these organic cation transporters. However, machine learning classifiers using 15 parameters allowed 69 to 87% correct prediction. The large number of substrates indicates a possibly broad role of multidrug and toxin extrusion (MATE) transporters in pharmacokinetics and drug interactions. - Source: PubMed
Publication date: 2025/06/13
Redeker Kyra-Elisa MariaKirsch NicolaiBoretius SusannTzvetkov MladenBrockmöller Jürgen