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- W4385233289 abstract "Platinum–acridine anticancer agents (PAs) containing acyclic (1 and 3) and heterocyclic (R)-3-aminopiperidine (2) and 2-iminopyrrolidine (4) based linker moieties were studied. Similar to 1, rigidified 2 shows a strong positive correlation between potency and SLC47A1 (multidrug and toxin extrusion protein 1, MATE1) gene expression levels across the NCI-60 panel of cancer cell lines. All derivatives show nanomolar activity in HepG2 (liver), NCI-H460 (lung), and MDA-MB-436 (breast), which express high levels of SLC47A1 (Cancer Cell Line Encyclopedia, CCLE). The PAs are up to 350-fold more potent than cisplatin. In a MATE1 inhibition assay, a significant reduction in activity is observed in the three cancer cell lines (4000-fold lower for HepG2). Molecular docking experiments provide insight into the compatibility of the structurally diverse set of PAs with MATE1-mediated transport. MATE1 is a predictive marker and actionable target that sensitizes cancer cells regardless of the tissue of origin to PAs." @default.
- W4385233289 created "2023-07-26" @default.
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- W4385233289 date "2023-07-25" @default.
- W4385233289 modified "2023-09-28" @default.
- W4385233289 title "Platinum–Acridine Agents with High Activity in Cancers Expressing the Solute Carrier MATE1 (<i>SLC47A1</i>)" @default.
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- W4385233289 doi "https://doi.org/10.1021/acsmedchemlett.3c00266" @default.
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