Search results for "ABCC1"

showing 4 items of 4 documents

Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

2021

Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1) is significantly hindering effective cancer chemotherapy. However, currently, no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically, mainly due to the inhibitor specificity, toxicity, and drug interactions. Here, we reported that three polyoxypregnanes (POPs) as the most abundant constituents of Marsdenia tenacissima (M. tenacissima) were novel ABCB1-modulatory pro-drugs, which underwent intestinal microbiota-mediated biotransformation in vivo to generate active metabolites. The metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells v…

ABCC1 ATP binding cassette subfamily C member 1IC50 half maximal inhibitory concentrationMultidrug resistancePharmacologyNADPH reduced nicotinamide adenine dinucleotide phosphateF bioavailabilitychemistry.chemical_compoundPCR polymerase chain reaction0302 clinical medicineMDR multidrug resistanceECL electrochemiluminescencet1/2 elimination half-lifeLC–MS liquid chromatography coupled with mass spectrometryN.D. not detectedGeneral Pharmacology Toxicology and PharmaceuticsBBB blood–brain barriermedia_commonATF3 activating transcription factor 30303 health sciencesChemistryABC ATP-binding cassetteNMPA National Medical Products AdministrationPXR pregnane X receptorSDS-PAGE sodium dodecyl sulfate-polyacrylamide gel electrophoresisHBSS Hankʹs balanced salt solutionABCB1Combination chemotherapyProdrugMarsdenia tenacissimaCmax peak concentrationPaclitaxelGAPDH glyceraldehyde-3-phosphate dehydrogenase030220 oncology & carcinogenesisBHI brain heart infusionOriginal ArticleAUC0–∞ area under plasma concentration vs. time curveMRT mean residence timeDrugmedia_common.quotation_subjectRM1-950Vd volume of distributionABCB1 ATP binding cassette subfamily B member 1UIC-2 mouse monoclonal ABCB1 antibodyABCG2 ATP binding cassette subfamily G member 2Combination chemotherapyCYP cytochrome P450 isozymePI propidium iodideTEER transepithelial electrical resistance03 medical and health sciencesPBS phosphate buffer salineFBS fetal bovine serumDox doxorubicinIn vivoPOP polyoxypregnanemedicine030304 developmental biologyEVOM epithelial tissue voltohmmeterTmax time for peak concentrationCancerLBE lowest binding energyPE phycoerythrinmedicine.diseaseMultiple drug resistancePolyoxypregnanePapp apparent permeabilityN.A. not applicableCancer cellH&E hematoxylin and eosinMDR1a multidrug resistance protein 1aTherapeutics. PharmacologyqPCR quantitative PCRM. tenacissima Marsdenia tenacissimaCL clearanceSD standard derivationActa Pharmaceutica Sinica B
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Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

2021

Adenosine-triphosphate-(ATP)-binding cassette (ABC) transport proteins are ubiquitously present membrane-bound efflux pumps that distribute endo- and xenobiotics across intra- and intercellular barriers. Discovered over 40 years ago, ABC transporters have been identified as key players in various human diseases, such as multidrug-resistant cancer and atherosclerosis, but also neurodegenerative diseases, such as Alzheimer���s disease (AD). Most prominent and well-studied are ABCB1, ABCC1, and ABCG2, not only due to their contribution to the multidrug resistance (MDR) phenotype in cancer, but also due to their contribution to AD. However, our understanding of other ABC transporters is limited…

ABCG2 (BCRP)Multitarget inhibitor (PANABC)Broad-spectrum modulatorPolypharmacologyActivationNeurosciences. Biological psychiatry. NeuropsychiatryAmyloid-beta (Aβ / Abeta)ABCA2ABCA5ArticleABCA7InductionABCB1 (P-gp)Pattern analysisDownregulationPET Tracer (PETABC)ABC transporterABCA1 (ABC1)Rational drug design and developmentAlzheimer’s diseaseRC321-571ABCC1 (MRP1)InhibitionFree neuropathology
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Measurement of cerebral ABCC1 transport activity in wild-type and APP/PS1-21 mice with positron emission tomography

2020

Previous data suggest a possible link between multidrug resistance-associated protein 1 (ABCC1) and brain clearance of beta-amyloid (Aβ). We used PET with 6-bromo-7-[11C]methylpurine ([11C]BMP) to measure cerebral ABCC1 transport activity in a beta-amyloidosis mouse model (APP/PS1-21) and in wild-type mice aged 50 and 170 days, without and with pretreatment with the ABCC1 inhibitor MK571. One hundred seventy days-old-animals additionally underwent [11C]PiB PET scans to measure Aβ load. While baseline [11C]BMP PET scans detected no differences in the elimination slope of radioactivity washout from the brain (kelim) between APP/PS1-21 and wild-type mice of both age groups, PET scans after MK…

Mice TransgenicNeuroimaging03 medical and health sciencesAmyloid beta-Protein PrecursorMice0302 clinical medicineMethylpurineAlzheimer Diseasemental disordersmedicinePresenilin-1Animals030304 developmental biology0303 health sciencesmedicine.diagnostic_testbiologyTransport activityChemistryWild typeOriginal ArticlesMolecular biologyMice Inbred C57BLDisease Models AnimalNeurologyPositron emission tomographyPositron-Emission TomographyABCC1biology.proteinFemaleNeurology (clinical)Multidrug Resistance-Associated Protein 1Multidrug Resistance-Associated ProteinsRadiopharmaceuticalsCardiology and Cardiovascular Medicine030217 neurology & neurosurgeryJournal of Cerebral Blood Flow & Metabolism
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2020

The efficiency of chemotherapy drugs can be affected by ATP-binding cassette (ABC) transporter expression or by their mutation status. Multidrug resistance is linked with ABC transporter overexpression. In the present study, we performed rare mutation analyses for 12 ABC transporters related to drug resistance (ABCA2, -A3, -B1, -B2, -B5, -C1, -C2, -C3, -C4, -C5, -C6, -G2) in a dataset of 18 cancer patients. We focused on rare mutations resembling tumor heterogeneity of ABC transporters in small tumor subpopulations. Novel rare mutations were found in ABCC1, but not in the other ABC transporters investigated. Diverse ABCC1 mutations were found, including nonsense mutations causing premature …

MutationbiologyNonsense mutationCancerATP-binding cassette transporterGeneral MedicineABCA2Drug resistancemedicine.diseasemedicine.disease_causeStop codonCancer researchmedicinebiology.proteinABCC1Cells
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