K145 is a selective, substrate-competitive and orally active SphK2 inhibitor with IC50 of 4.3 μM and Ki of 6.4 μM.It is inactive against SphK1 and other protein kinases,it induces apoptosis and has potent 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.
Cell Viability Assay
Cell Line:
< td class="col2"> U937 cells
Concentration:
0 μM, 4 μM, 6 μM , 8 μM, 10 μM
Incubation Time:
24 hours, 48 hours, 72 hours
td>
Result:
Significantly inhibited the growth of U937 cells in a concentration-dependent manner.
Apoptosis Analysis
Cell Line:
U937 cells
Concentration:
10 μM
Incubation Time:
24 hours
Result:
Significantly induced apoptosis in U937 cells.
Western Blot Analysis < /p>
Cell Line:
U937 cells
Concentration:
4 μM, 8 μM
Incubation Time: < /td>
3 hours
Result:
Phosphorylated ERK and Akt wer e 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.
Animal Model:
BALB/c-nu mice injected with U937 cells
Dosage:
50 mg/kg
Administration:
Oral gavage; daily; for 15 days
Result:
Oral gavage; daily; for 15 daysInhibited the growth of U937 tumors at 50 mg/kg dose and no apparent toxicity was observed.
