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Beschreibung

A cell-permeable imidazothiazolyl-chromenone compound that reduces cellular midkine/MDK protein level in H441 lung adenocarcinoma cells in a dose-dependent manner (by >90% in 48 h at 25 nM) via a yet unidentified mechanism. Shown to inhibit the viability of MDK-positive HEK293, H441, and H520 cells (by &ge,60% at 500 nM in 48 h), but not MDK-negative NHLF or HEK293 (by <15% at 500 nM in 48 h), via apoptosis induction as a result of PI 3-K/AKT signaling inhibition. Intraperitoneal injection is reported to be efficacious in retarding H441 tumor expansion in mice (9 mg/kg, 3X to 5X per wk) in vivo., A cell-permeable imidazothiazolyl-chromenone compound that reduces cellular midkine/MDK protein level in H441 lung adenocarcinoma cells in a dose-dependent manner (by >90% in 48 h at 25 nM) via a yet unidentified mechanism, while exhibiting little effect toward cellular level of PTN or VEGF. Shown to inhibit the viability of MDK-positive HEK293, H441, and H520 cells (by &ge,60% at 500 nM in 48 h), but not MDK-negative NHLF (normal human lung fibroblast) or HEK293 (by <15% at 500 nM in 48 h), via apoptosis induction as a result of PI 3-K/AKT signaling, but not Erk or p38, pathway inhibition. Intraperitoneal injection is reported to be efficacious in retarding H441 tumor expansion in mice (75% vs 400% increase in tumor volume in 10 d with or without treatment, 3 to 5 times 9 mg/kg i.p. dosing per wk) in vivo.