Sökning: id:"swepub:oai:DiVA.org:uu-423990" >
Expanding the Efflu...
Expanding the Efflux In Vitro Assay Toolbox : A CRISPR-Cas9 Edited MDCK Cell Line with Human BCRP and Completely Lacking Canine MDR1
-
- Wegler, Christine (författare)
- Uppsala universitet,Institutionen för farmaci,Drug Delivery Research Group; Uppsala University Drug Optimization and Pharmaceutical Profiling Platform (UDOPP)
-
- Gazit, Meryem (författare)
- Uppsala universitet,Institutionen för farmaci,Drug Delivery Research Group
-
- Issa, Karolina (författare)
- Uppsala universitet,Institutionen för farmaci,Drug Delivery Research Group
-
visa fler...
-
- Subramaniam, Sujay (författare)
- Uppsala universitet,Institutionen för farmaci,Drug Delivery Research Group
-
- Artursson, Per (författare)
- Uppsala universitet,Institutionen för farmaci,Drug Delivery Research Group; Uppsala University Drug Optimization and Pharmaceutical Profiling Platform (UDOPP)
-
- Karlgren, Maria (författare)
- Uppsala universitet,Institutionen för farmaci,Drug Delivery Research Group; Uppsala University Drug Optimization and Pharmaceutical Profiling Platform (UDOPP)
-
visa färre...
-
(creator_code:org_t)
- Elsevier, 2021
- 2021
- Engelska.
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 110:1, s. 388-396
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://uu.diva-port... (primary) (Raw object)
-
http://jpharmsci.org...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- The Breast Cancer Resistance Protein (BCRP) is a key transporter in drug efflux and drug-drug interactions. However, endogenous expression of Multidrug Resistance Protein 1 (MDR1) confounds the interpretation of BCRP-mediated transport in in vitro models. Here we used a CRISPR-Cas9 edited Madin-Darby canine kidney (MDCK) II cell line (MDCKcMDR1-KO) for stable expression of human BCRP (hBCRP) with no endogenous canine MDR1 (cMDR1) expression (MDCK-hBCRPcMDR1-KO). Targeted quantitative proteomics verified expression of hBCRP, and global analysis of the entire proteome corroborated no or very low background expression of other drug transport proteins or metabolizing enzymes. This new cell line, had similar proteome like MDCKcMDR1-KO and a previously established, corresponding cell line overexpressing human MDR1 (hMDR1), MDCK-hMDR1cMDR1-KO. Functional studies with MDCK-hBCRPcMDR1-KO confirmed high hBCRP activity. The MDCK-hBCRPcMDR1-KO cell line together with the MDCK-hMDR1cMDR1-KO easily and accurately identified shared or specific substrates of the hBCRP and the hMDR1 transporters. These cell lines offer new, improved in vitro tools for the assessment of drug efflux and drug-drug interactions in drug development.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- ATP-binding cassette (ABC) transporter(s)
- Breast cancer resistance protein (BCRP)
- Drug transport
- Efflux pumps
- MDCK cells
- Membrane transporter
- P-glycoprotein (P-gp)
- Permeability
- Proteomics
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas