K145 hydrochloride is a selective, substrate-competitive and orally active SphK2 inhibitor with an IC 50 of 4.3 µM and a K i of 6.4 µM. K145 hydrochloride is inactive against SphK1 and other protein kinases. K145 hydrochloride induces cell apoptosis and has potently antitumor activity
In Vitro
K145 (0-10 µM; 24-72 hours; U937 cells) treatment significantly inhibits the growth of U937 cells in a concentration-dependent manner. K145 (10 µM; 24 hours; U937 cells) treatment significantly induces apoptosis in U937 cells. K145 (4-8 µM; 3 hours; U937 cells) treatment decreases the phosphorylation of ERK and Akt. Treatment with K145 (10 µM) causes a decrease of total cellular S1P without significant effects on ceramide levels. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: U937 cells Concentration: 0 µM, 4 µM, 6 µM, 8 µM, 10 µM Incubation Time: 24 hours, 48 hours, 72 hours Result: Significantly inhibited the growth of U937 cells in a concentration-dependent manner. Apoptosis AnalysisCell Line: U937 cells Concentration: 10 µM Incubation Time: 24 hours Result: Significantly induced apoptosis in U937 cells. Western Blot AnalysisCell Line: U937 cells Concentration: 4 µM, 8 µM Incubation Time: 3 hours Result: Phosphorylated ERK and Akt were decreased.
In Vivo
K145 (50 mg/kg; oral gavage; daily; for 15 days; BALB/c-nu mice) treatment significantly inhibits the growth of U937 tumors in nude mice . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: BALB/c-nu mice injected with U937 cells Dosage: 50 mg/kg Administration: Oral gavage; daily; for 15 days Result: Inhibited the growth of U937 tumors at 50 mg/kg dose and no apparent toxicity was observed.
