Identifikace nových účinných inhibitorů kináz CLK a HIPK s optimálním in vitro a in vivo profilem
| Title in English | Identification of new potent inhibitors of CLK and HIPK kinases with optimal in vitro and in vivo profiles. |
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| Authors | |
| Year of publication | 2018 |
| MU Faculty or unit | |
| Description | Compound VN339 is highly selective and does not inhibit virtually any other protein kinases at pharmacologically active concentrations. Compounds that showed attractive activity in the in vitro primary biochemical assay were subsequently profiled in a cell assay in MCF7 tumor cells. To confirm the effective inhibition of CLK kinases in the cell, selected compounds were also profiled in a NanoBRET assay that is specific for cellular inhibition of CLK kinases. The most potent compound, VN339 (= MU1210), was prepared as a soluble dihydrochloride (VN1173), which went into in vivo studies where the pharmacokinetic profile in mice was determined: it was found that at 10mg / kg (IP) the concentration of this compound was sufficient ( pharmacologically active) for two hours. Compound VN339 is highly selective and does not inhibit virtually any other protein kinases at pharmacologically active concentrations. |
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