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• W4307846908 abstract "The Ca2+ activated K+ channel KCa 3.1 is overexpressed in several human tumor cell lines, e. g. clear cell renal carcinoma, prostate cancer, non-small cell lung cancer. Highly aggressive cancer cells use this ion channel for key processes of the metastatic cascade such as migration, extravasation and invasion. Therefore, small molecules, which are able to image this KCa 3.1 channel in vitro and in vivo represent valuable diagnostic and prognostic tool compounds. The [18 F]fluoroethyltriazolyl substituted senicapoc was used as positron emission tomography (PET) tracer and showed promising properties for imaging of KCa 3.1 channels in lung adenocarcinoma cells in mice. The novel senicapoc BODIPY conjugates with two F-atoms (9 a) and with a F-atom and a methoxy moiety (9 b) at the B-atom led to the characteristic punctate staining pattern resulting from labeling of single KCa 3.1 channels in A549-3R cells. This punctate pattern was completely removed by preincubation with an excess of senicapoc confirming the high specificity of KCa 3.1 labeling. Due to the methoxy moiety at the B-atom and the additional oxyethylene unit in the spacer, 9 b exhibits higher polarity, which improves solubility and handling without reduction of fluorescence quantum yield. Docking studies using a cryo-electron microscopy (EM) structure of the KCa 3.1 channel confirmed the interaction of 9 a and 9 b with a binding pocket in the channel pore." @default.
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• W4307846908 date "2022-11-22" @default.
• W4307846908 modified "2023-10-16" @default.
• W4307846908 title "Imaging of K_Ca3.1 Channels in Tumor Cells with PET and Small‐Molecule Fluorescent Probes" @default.
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• W4307846908 doi "https://doi.org/10.1002/cmdc.202200551" @default.
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