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| http://dx.doi.org/10.3389/fphar.2023.1182571 | DOI Listing |
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Structural insights into binding-site access and ligand recognition by human ABCB1.
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ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, how it is able to recognize and transport a wide range of diverse substrates remains poorly understood. Here we present cryo-EM structures of lipid-embedded human ABCB1 in conformationally distinct apo-, substrate-bound, inhibitor-bound, and nucleotide-trapped states at 3.
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Drug resistance is a major challenge in cancer therapy, and the expression of efflux pumps such as P-glycoprotein (P-gp, ABCB1) often correlates with poor prognosis in various tumors, including glioblastoma (GB). Considering that different roles for these proteins have been established in the biology of various tumors, this study aimed to investigate the functions of P-gp in GB-derived cells by evaluating its survival, migratory, and apoptosis-regulating capabilities, as well as its potential as a liquid biopsy biomarker. P-gp expression was diminished via siRNA to determine its exact role in GB biology.
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Cynanchum wallichii (CW) is a traditional Chinese medicine which is widely used for treating arthrophlogosis, traumatic injury, and other conditions. Herein, we investigate the effects and mechanisms of CW and its bioactive constituent CW1 in reversing docetaxel (DTX) resistance in prostate cancer (PCa) cells. We investigated the reversal effects of CW and its bioactive constituent CW1 on 22Rv1/DTX cells in vitro and in vivo.
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Division of Systems Pharmacology and Pharmacy, Leiden Academic Center for Drug Research, Leiden University, Einsteinweg 55, Leiden, 2333 CC, The Netherlands.
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