Drug efflux by P-glycoprotein (P-gp, ABCB1) is considered as a major obstacle for brain drug delivery for small molecules. P-gp-expressing cell monolayers are used for screening of new drug candidates during early states of drug development. It is, however, uncertain how well the in vitro studies can predict the in vivo P-gp mediated efflux at the blood-brain barrier (BBB). We previously developed a novel cell line of porcine origin, the iP-gp cell line, with high transepithelial resistance and functional expression of human P-gp. The aim of the present study was to evaluate the applicability of the cell line for screening of P-gp interactions of novel drug candidates. For this purpose, bidirectional fluxes of 14 drug candidates were measured in iP-gp cells and in MDCK-MDR1 cells, and compared with pharmacokinetic data obtained in male C57BL/6 mice. The iP-gp cells formed extremely tight monolayers (>15 000 Ω∙cm) as compared to the MDCK- MDR1 cells (>250 Ω∙cm) and displayed lower P values. The efflux ratios obtained with iP-gp and MDCK-MDR1 monolayers correlated with K values from the in vivo studies, where compounds with the lowest K generally displayed the highest efflux ratios. 12 of the tested compounds displayed a poor BBB penetration in mice as judged by K less than 1. Of these compounds, nine compounds were categorized as P-gp substrates in the iP-gp screening, whereas analysis of data estimated in MDCK-MDR1 cells indicated four compounds as potential substrates. The results suggest that the iP-gp cell model may be a sensitive and useful screening tool for drug screening purposes to identify possible substrates of human P-glycoprotein.
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http://dx.doi.org/10.1016/j.ejpb.2021.10.006 | DOI Listing |
Arch Dermatol Res
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Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
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Department of Hematology, Navy Medical Center of PLA, Naval Medical University, No. 338 West Huaihai Road, Changning District, Shanghai, 200052, China.
Multiple myeloma(MM) remains incurable with high relapse and chemoresistance rates. Differentially expressed genes(DEGs) between newly diagnosed myeloma and secondary plasma cell leukemia(sPCL) were subjected to a weighted gene co-expression network analysis(WGCNA). Drug resistant myeloma cell lines were established.
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January 2025
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Background: Jianwei Xiaoshi oral liquid (JWXS), a classical traditional prescription comprising various edible medicinal plants, has demonstrated significant efficacy in treating paediatric indigestion. It originates from Jianpi Pill, which is developed in the Ming Dynasty and nourishes the spleen and regulates gastrointestinal function. However, the specific molecular mechanisms involved remain unclear.
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Department of Molecular Pathology, IRCCS Neuromed, Pozzilli, Italy.
Metabotropic glutamate (mGlu) receptors are candidate drug targets for therapeutic intervention in Parkinson's disease (PD). Here we focused on mGlu3, a receptor subtype involved in synaptic regulation and neuroinflammation. mGlu3 mice showed an enhanced nigro-striatal damage and microglial activation in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
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January 2025
Pharmaceutical Microbiology Department, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt.
Carbapenem-resistant Klebsiella pneumoniae poses a severe risk to global public health, necessitating the immediate development of novel therapeutic strategies. The current study aimed to investigate the effectiveness of the green algae Arthrospira maxima (commercially known as Spirulina) both in vitro and in vivo against carbapenem-resistant K. pneumoniae.
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